Intellectual disability
Gene: PHF12

PHF12 (PHD finger protein 12)
EnsemblGeneIds (GRCh38): ENSG00000109118
EnsemblGeneIds (GRCh37): ENSG00000109118
PHF12 is in 2 panels

2 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are numerous individuals reported in literature in large cohort studies of intellectual disability, ASD, and developmental disorders patients, harbouring heterozygous de novo variants in PHF12. The association between PHF12 and a complex neurodevelopmental disorder was classified as Definitive by the Intellectual Disability and Autism ClinGen Expert Panel (Feb 2025). Based on available evidence this gene should be promoted to Green for Intellectual disability.
Created: 10 Feb 2026, 4:59 p.m. | Last Modified: 10 Feb 2026, 4:59 p.m.

Panel Version: 9.254

The below publication information is taken from ClinGen evidence summary: https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_329aa190-d20e-4f6b-9c85-58242a8a2d33-2025-02-19T110000.000Z?page=1&size=25&search=

Lelieveld SH, et al., 2016, PMID: 27479843
Cohort (Radboud University Medical Center) with unexplained intellectual disability, no detailed clinical information available. Exome seq revealed de novo heterozygous NM_001033561.2(PHF12):c.425C>A (p.Ser142Ter).

Deciphering Developmental Disorders Study, 2017, PMID: 28135719
DDD Study cohort with severe undiagnosed developmental disorders, no detailed clinical information available. Exome seq revealed de novo heterozygous NM_001033561.2(PHF12):c.2645del (p.Pro882GlnfsTer30).

C Yuen RK, et al., 2017, PMID: 28263302
ASD cohort (MSSNG), no detailed clinical information available. Method: Whole genome shotgun sequencing. Het for de novo NM_001033561.2(PHF12):c.1091dup (p.Asn365Ter).

Kaplanis J, et al., 2020, PMID: 33057194
31,058 parent-offspring trios of individuals with developmental disorders.
Cohort (GeneDx) with developmental disorders, no detailed clinical information available: GDX 15850 het for de novo NM_001033561.2(PHF12):c.2360-1G>A
DDD Study cohort: DDD13k.08251 - het for de novo NM_001033561.2(PHF12):c.1970C>G (p.Ser657Ter)
DDD Study cohort: DDD13k.05315 - het for de novo NM_001033561.2(PHF12):c.862C>T (p.Gln288Ter)
Cohort (Radboud University Medical Center) with unexplained intellectual disability: de novo heterozygous NM_001033561.2(PHF12):c.2542-2A>C

Functional evidence:
PMID: 27956701 Graveline et al., 2017 - Phf12 (Pf1) -/- mouse embryos had global growth retardation and impaired development of skeleton, associated skeletal muscle, and brain. They died mid- to late-gestation due to developmental defects including edema and internal hemorrhage. Heterozygous Pf1+/- mice developed normally.

PHF12 is not yet linked to a disease entity in OMIM (accessed 10th Feb 2026). The gene-disease association between PHF12 and AD complex neurodevelopmental disorder (MONDO:0100038) was classified as Definitive by the Intellectual Disability and Autism ClinGen Expert Panel (Feb 2025). Gene2Phenotype rated its association with PHF12-related developmental disorder as Strong.
Created: 10 Feb 2026, 4:42 p.m. | Last Modified: 10 Feb 2026, 4:55 p.m.

Panel Version: 9.253

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
complex neurodevelopmental disorder, MONDO:0100038

Publications

Created: 10 Feb 2026, 4:42 p.m.
Last Modified: 10 Feb 2026, 4:55 p.m.
Panel version: 9.253

Sophie Ellis (North East & Yorkshire Genomic Laboratory Hub)

Green List (high evidence)

ClinGen Definitive Classification - 02/19/2025
Sources: ClinGen
Created: 13 Jan 2026, 11:32 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice

Created: 13 Jan 2026, 11:32 a.m.

Panel version: 9.234

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Amber

Phenotypes

complex neurodevelopmental disorder, MONDO:0100038

Tags

Q1_26_promote_green Q1_26_NHS_review

Clinvar variants

Variants in PHF12

Penetrance

unknown

Publications

Mode of Pathogenicity

Other

Panels with this gene