Summary Statistics:
ASD Reports: 13
Recent Reports: 2
Annotated variants: 33
Associated CNVs: 9
Evidence score: 3
Gene Score: S
Relevance to Autism
An in-frame deletion variant in PHF8 was found to segregate with high-functioning autism without other clinical features in a multiplex ASD family (Nava et al., 2012). Mutations in this gene are associated with a syndromic form of X-linked intellectual disability (Siderius type X-linked syndromic mental retardation; OMIM 300263); behavioral abnormalities and stereotypic movements have been observed in some individuals with this disorder (Laumonnier et al., 2005; Abidi et al., 2007; Koivisto et al., 2007; Redin et al., 2014; Deciphering Developmental Disorders Study 2015). Sobering et al., 2022 presented 16 individuals with Siderious X-linked intellectual disability syndrome caused by loss-of-function variants in the PHF8 gene from 11 families and found that all affected individuals exhibited developmental delay, and all but two had borderline to severe intellectual disability, autism spectrum disorder (ASD) was reported in seven of these individuals.
Molecular Function
The protein encoded by this gene is a histone lysine demethylase that preferentially acts on histones in the monomethyl or dimethyl states. The encoded protein requires Fe(2+) ion, 2-oxoglutarate, and oxygen for its catalytic activity. The protein has an N-terminal PHD finger and a central Jumonji C domain. This gene is thought to function as a transcription activator. Defects in this gene are a cause of syndromic X-linked Siderius type intellectual disability (MRXSSD).
References
Primary
Analysis of the chromosome X exome in patients with autism spectrum disorders identified novel candidate genes, including TMLHE.
ASD
ID
Support
Large-scale discovery of novel genetic causes of developmental disorders.
DD, ADHD
Microcephaly
Support
Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.
ID
Support
New Candidates for Autism/Intellectual Disability Identified by Whole-Exome Sequencing
ASD, DD, ID
Support
Screening of mutations in the PHF8 gene and identification of a novel mutation in a Finnish family with XLMR and cleft lip/cleft palate.
ID
Support
A loss-of-function variant in SUV39H2 identified in autism-spectrum disorder causes altered H3K9 trimethylation and dysregulation of protocadherin β-cluster genes in the developing brain
ASD
Support
A novel mutation in the PHF8 gene is associated with X-linked mental retardation with cleft lip/cleft palate.
ID
Support
A recurrent PJA1 variant in trigonocephaly and neurodevelopmental disorders
ASD, DD
Support
Targeted Next-Generation Sequencing in Patients with Suggestive X-Linked Intellectual Disability.
ID
Support
Characterization of intellectual disability and autism comorbidity through gene panel sequencing.
ID, ASD or autistic traits
Highly Cited
Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate.
ID
Recent Recommendation
Variants in PHF8 cause a spectrum of X-linked neurodevelopmental disorders and facial dysmorphology
DD, ID
ASD, ADHD, epilepsy/seizures
Recent Recommendation
JMJD-1.2/PHF8 controls axon guidance by regulating Hedgehog-like signaling.
GEN456R001
inframe_deletion
c.2904_2906del
p.Ser969del
Familial
Maternal
Multiplex
GEN456R002
splice_site_variant
del(ACAGGTCTTCCC)
Familial
Maternal
Multi-generational
GEN456R003
stop_gained
c.631C>T
p.Arg211Ter
Familial
Maternal
Multi-generational
GEN456R004
stop_gained
c.529T>A
p.Ser177Thr
De novo
GEN456R005
missense_variant
c.836C>T
p.Phe279Ser
Familial
Maternal
Multiplex
GEN456R006
frameshift_variant
c.738dup
p.Arg247SerfsTer17
Familial
Maternal
Multi-generational
GEN456R007
splice_site_variant
c.1249+5G>C
Familial
Maternal
Simplex
GEN456R008
missense_variant
c.2794T>C
p.Cys932Arg
Familial
Maternal
GEN456R009
stop_gained
c.252C>A
p.Tyr84Ter
Familial
Maternal
Simplex
GEN456R010
missense_variant
c.2972A>G
p.Asn991Ser
Familial
Maternal
Simplex
GEN456R011
missense_variant
c.*1112G>C
Familial
Maternal
GEN456R012
missense_variant
c.*1101G>A
Unknown
GEN456R013
missense_variant
c.2475G>C
p.Glu825Asp
Unknown
GEN456R014
missense_variant
c.2239G>A
p.Glu747Lys
Familial
Maternal
GEN456R015
missense_variant
c.264C>A
p.Asn88Lys
Unknown
GEN456R016
missense_variant
c.124G>T
p.Val42Leu
Familial
Maternal
GEN456R017
inframe_deletion
c.2190_2192del
p.Leu731del
De novo
Simplex
GEN456R018
inframe_deletion
p.Gly316_Arg380del
Familial
Maternal
GEN456R019
splice_site_variant
c.704+1G>A
De novo
Simplex
GEN456R020
stop_gained
c.862C>T
p.Gln288Ter
Familial
Maternal
Multiplex
GEN456R021
frameshift_variant
c.2104del
p.Glu702ArgfsTer163
Familial
Maternal
Simplex
GEN456R022
stop_gained
c.1027C>T
p.Gln343Ter
Familial
Maternal
Extended multiplex
GEN456R023
splice_site_variant
c.1731-2A>G
Familial
Maternal
Multiplex (monozygotic twins)
GEN456R024
splice_site_variant
c.1731-2A>G
Familial
Maternal
Simplex
GEN456R025
splice_site_variant
c.1627-1G>A
De novo
GEN456R026
frameshift_variant
c.846dup
p.His283SerfsTer3
Familial
Maternal
GEN456R027
frameshift_variant
c.2868dup
p.Thr957HisfsTer19
Familial
Maternal
GEN456R028
frameshift_variant
c.2073_2074insTG
p.Glu692TrpfsTer174
De novo
Simplex
GEN456R029
inframe_deletion
c.294-1820_597-603del
Familial
Maternal
Simplex
GEN456R030
missense_variant
c.143A>G
p.Tyr48Cys
Familial
Maternal
GEN456R031
missense_variant
c.257C>T
p.Thr86Met
Familial
Maternal
Multiplex
GEN456R032
missense_variant
c.808C>T
p.Arg270Cys
Familial
Maternal
GEN456R033
missense_variant
c.1150G>A
p.Glu384Lys
Familial
Maternal
No Common Variants Available
X
Deletion-Duplication
25
X
Deletion-Duplication
21
No Animal Model Data Available
Summary Statistics:
Total Interactions: 35
Total Publications: 18
Show all nodes
Hide non-ASD
Interactor Symbol
Interactor Name
Interactor Organism
Entrez ID
Uniprot ID
Interaction Type
Evidence
Reference
ANAPC1
anaphase promoting complex subunit 1
64682
Q9H1A4
TAP; MS; IP/WB
Lim HJ , et al. 2013
ANAPC2
anaphase promoting complex subunit 2
29882
Q9UJX6
TAP; MS; IP/WB
Lim HJ , et al. 2013
ANAPC4
anaphase promoting complex subunit 4
29945
Q9UJX5
TAP; MS; IP/WB
Lim HJ , et al. 2013
ANAPC5
anaphase promoting complex subunit 5
51433
Q9UJX4
TAP; MS; IP/WB
Lim HJ , et al. 2013
ANAPC7
anaphase promoting complex subunit 7
51434
Q9UJX3
TAP; MS; IP/WB
Lim HJ , et al. 2013
APP
amyloid beta (A4) precursor protein
351
P05067
Protein microarray
Olh J , et al. 2011
ASH2L
ash2 (absent, small, or homeotic)-like (Drosophila)
9070
Q9UBL3
IP/WB
Feng W , et al. 2010
CCNA2
cyclin A2
890
P20248
IP; LC-MS/MS
Huttlin EL , et al. 2015
CDC16
cell division cycle 16
8881
Q13042
TAP; MS; IP/WB
Lim HJ , et al. 2013
CDC20
cell division cycle 20
991
Q12834
TAP; MS; IP/WB
Lim HJ , et al. 2013
CDC23
cell division cycle 23
8697
Q9UJX2
TAP; MS; IP/WB
Lim HJ , et al. 2013
CDC26
cell division cycle 26
246184
Q8NHZ8
TAP; MS; IP/WB
Lim HJ , et al. 2013
CDC27
cell division cycle 27
996
G3V1C4
TAP; MS; IP/WB
Lim HJ , et al. 2013
CHD8
chromodomain helicase DNA binding protein 8
57680
Q9HCK8
ChIP-chip
Subtil-Rodrguez A , et al. 2013
Dlg4
DLG4discs, large homolog 4 (Drosophila)
1742
P78352
Peptide microarray
Arbuckle MI , et al. 2010
FMR1
fragile X mental retardation 1
2332
G8JLE9
PAR-CLIP
Ascano M Jr , et al. 2012
FZR1
fizzy/cell division cycle 20 related 1 (Drosophila)
51343
Q9UM11
TAP; MS; IP/WB
Lim HJ , et al. 2013
HCFC1
host cell factor C1 (VP16-accessory protein)
3054
P51610
ChIP; IP/WB
Liu W , et al. 2010
HIST1H3A
histone cluster 1, H3a
8350
P68431
IP/WB
Feng W , et al. 2010
HIST1H4A
histone cluster 1, H4a
8359
B2R4R0
GST; IP/WB
Qi HH , et al. 2010
HIST3H3
histone cluster 3, H3
8290
Q16695
MS
Bartke T , et al. 2010
MAGEA10
Melanoma-associated antigen 10
4109
P43363
IP; LC-MS/MS
Huttlin EL , et al. 2015
MAML1
mastermind-like 1 (Drosophila)
9794
Q92585
ChIP; IP/WB
Yatim A , et al. 2012
NOTCH1
notch 1
4851
P46531
MS
Yatim A , et al. 2012
PHF8
PHD finger protein 8
23133
Q9UPP1
TAP; MS; IP/WB
Lim HJ , et al. 2013
POLR2A
polymerase (RNA) II (DNA directed) polypeptide A, 220kDa
5430
P24928
ChIP; IP/WB
Fortschegger K , et al. 2010
POLR2C
polymerase (RNA) II (DNA directed) polypeptide C, 33kDa
5432
P19387
ChIP; IP/WB
Fortschegger K , et al. 2010
RARA
retinoic acid receptor, alpha
5914
P10276
FRET
Qiu J , et al. 2010
RBPJ
recombination signal binding protein for immunoglobulin kappa J region
3516
Q06330
ChIP; IP/WB
Yatim A , et al. 2012
RPAP1
RNA polymerase II associated protein 1
26015
Q9BWH6
LC-MS/MS
Jeronimo C , et al. 2007
SUMO1
SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae)
7341
P63165
LC-MS/MS
Matafora V , et al. 2009
SUMO2
SMT3 suppressor of mif two 3 homolog 2 (S. cerevisiae)
6613
P61956
MS
Ouyang J , et al. 2009
UBC
ubiquitin C
7316
P63279
LC-MS/MS
Danielsen JM , et al. 2010
WDR5
WD repeat domain 5
609012
N/A
IP/WB
Feng W , et al. 2010
ZNF711
zinc finger protein 711
7552
Q6PK66
IP/WB
Kleine-Kohlbrecher D , et al. 2010