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Intellectual disability

Gene: ZNF148

Amber List (moderate evidence)
ZNF148 (zinc finger protein 148)
EnsemblGeneIds (GRCh38): ENSG00000163848
EnsemblGeneIds (GRCh37): ENSG00000163848
OMIM: 601897, Gene2Phenotype
ZNF148 is in 3 panels

6 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are now 27 unrelated individuals reported in literature with heterozygous ZNF148 variants and a syndromic neurodevelopmental disorder. Intellectual disability was the most consistent feature among all patients. Hence, ZNF148 can now be promoted to Green on this panel.
Created: 2 Nov 2026, 4:41 p.m. | Last Modified: 2 Nov 2026, 4:41 p.m.
Panel Version: 11.75
PMID: 37580113 Szakszon et al., 2024
Report of 22 previously unreported individuals with heterozygous ZNF148 variants and developmental delay (particularly speech development), postnatal growth retardation, microcephaly and facial dysmorphism. 2 variants were inherited from an affected parent, otherwise de novo.
Phenotypic spectrum of all 27 reported individuals: microcephaly <3pct (12/25), short stature <3pct (16/26), recurrent or severe infections (11/24), limb anomalies (18/25 - relatively mild: deep palmar creases, limited joint mobility, short hands and feet, pes planus), intellectual disability (23/25, severity not stated), corpus callosum hypoplasia (7/19), and other more variable features.
25/27 individuals harboured a variant in exon 9 of ZNF148; 22/24 were confirmed to be de novo.

PMID: 36444493 Miao et al., 2023
Report of a male patient with intellectual disability, ASD, and ADHD. The patient had a de novo het variant c.1818dupC (p.Lys607Glnfs*11) in ZNF148. His WISC-R Intelligence test at 7 yrs 11 months showed IQ total of below 46 (moderate ID). NO microcephaly or callosal developmental abnormalities present.

ZNF148 is associated with AD Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, OMIM:617260 in OMIM (accessed 2nd Nov 2026).
Created: 2 Nov 2026, 4:37 p.m. | Last Modified: 2 Nov 2026, 4:44 p.m.
Panel Version: 11.75

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, OMIM:617260; global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, MONDO:0014994

Publications

Created: 2 Nov 2026, 4:37 p.m.
Last Modified: 2 Nov 2026, 4:44 p.m.
Panel version: 11.75

Arina Puzriakova (Genomics England Curator)

I don't know

Associated with phenotype in OMIM and a 'probable' gene for ZNF148-related developmental disorder (monoallelic) in Gene2Phenotype.

Maintaining Amber rating in view of the single study (PMID: 27964749) reporting 4 unrelated cases with variants in various genes including ZNF148. Despite ZNF148 likely representing the most promising candidate, as outlined in the recent review by Zornitza Stark, contribution of variants identified in other genes can not be definitively ruled out. No functional studies of ZNF148 variants have been undertaken, and no further studies have been recently published linking ZNF148 to a neurodevelopmental phenotype.
Created: 27 Oct 2020, 10:37 a.m. | Last Modified: 27 Oct 2020, 10:37 a.m.
Panel Version: 3.485

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, 617260

Publications

Created: 27 Oct 2020, 10:37 a.m.
Last Modified: 27 Oct 2020, 10:37 a.m.
Panel version: 3.485

Zornitza Stark (Australian Genomics)

Green List (high evidence)

The ZNF148 variants are truncating and de novo, and meet criteria for pathogenic variant using the ACMG criteria, provided we accept there is gene-disease association. The phenotype reported is also relatively consistent, strengthening the case.

By contrast, the additional variants mentioned by the authors are relatively weak:
The maternally inherited COL3A1 variant is discordant for the observed phenotype, maternally inherited (mother asymptomatic) and has a population frequency consistent with benign variation.
The PDCD4 homozygous variant has been assessed as likely benign by the authors.
The de novo missense variants in SART3 and TCERG1 are firmly VOUS as there is no evidence for Mendelian gene-disease association for these two genes and they have no other compelling features.

We have therefore rated this gene Green.
Created: 4 Mar 2020, 1:56 a.m. | Last Modified: 4 Mar 2020, 1:56 a.m.
Panel Version: 3.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, 617260

Publications

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

Created: 4 Mar 2020, 1:56 a.m.
Last Modified: 4 Mar 2020, 1:56 a.m.
Panel version: 3.3

Rebecca Foulger (Genomics England curator)

I don't know

In 4 unrelated children with global developmental delay, hypoplastic corpus callosum, and dysmorphic facies (MIM:617260), PMID:27964749 (2016) identified 4 different de novo heterozygous truncating mutations in the ZNF148 gene. However, variants in additional genes were detected in 3 of the patients, and therefore further ZNF148 cases are required to support ID causation.
Created: 31 Oct 2017, 9:24 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, 617260

Publications

Created: 31 Oct 2017, 9:24 a.m.

Panel version: Imported from Intellectual disability update Oct 2017 panel version 0.4

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_manual . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 8:58 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

  • Manual assessment of Genes of interest from literature searches and personal communication

Created: 2 Aug 2017, 11:28 p.m.

Panel version: 1.354

Louise Daugherty (Genomics England Curator)

Comment on list classification: This gene is from an expert list and needs further assessment by the Genomics England curation team to access inclusion and pertinence to this panel.
Created: 28 Jul 2017, 5:13 p.m.
Created: 28 Jul 2017, 5:13 p.m.

Panel version: 1.352

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, OMIM:617260
  • global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, MONDO:0014994
Tags
Q4_26_promote_green
OMIM
601897
Clinvar variants
Variants in ZNF148
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

2 Nov 2026, Gel status: 2

Set Phenotypes

Ida Ertmanska (Genomics England Curator)

Phenotypes for gene: ZNF148 were changed from Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, 617260 to Global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, OMIM:617260; global developmental delay, absent or hypoplastic corpus callosum, and dysmorphic facies, MONDO:0014994

2 Nov 2026, Gel status: 2

Set publications

Ida Ertmanska (Genomics England Curator)

Publications for gene: ZNF148 were set to 27964749

2 Nov 2026, Gel status: 2

Set mode of inheritance

Ida Ertmanska (Genomics England Curator)

Mode of inheritance for gene: ZNF148 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

2 Nov 2026, Gel status: 2

Added Tag

Ida Ertmanska (Genomics England Curator)

Tag Q4_26_promote_green tag was added to gene: ZNF148.

12 Mar 2018, Gel status: 2

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

29 Nov 2017, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene ZNF148 was set to ['27964749']

28 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

27 Jul 2017, Gel status: 0

Added New Source

BRIDGE consortium (NIHRBR-RD)

ZNF148 was added to Intellectual disabilitypanel. Sources: BRIDGE study SPEED NEURO Tier1 Gene

27 Jul 2017, Gel status: 0

Created

BRIDGE consortium (NIHRBR-RD)

ZNF148 was created by BRIDGE