WDHD1

protein-coding

WD repeat and HMG-box DNA binding protein 1, the group of WD repeat domain containing

Gene summary

The protein encoded by this gene contains multiple N-terminal WD40 domains and a C-terminal high mobility group (HMG) box. WD40 domains are found in a variety of eukaryotic proteins and may function as adaptor/regulatory modules in signal transduction, pre-mRNA processing and cytoskeleton assembly. HMG boxes are found in many eukaryotic proteins involved in chromatin assembly, transcription and replication. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_007086.4

Inheritance

—

ClinVar variants

U:145B:19

Top phenotype

WDHD1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr14:54,938,949-55,027,105

External References & Databases

Ensembl (ENSG00000198554)

Transcript & Mutation Effects

hg38 • Region Span ~88.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WDHD1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 147

not providedTotal: 14

WDHD1-related disorderTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007086.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	1 clinvar	4 clinvar	7
missense			139 clinvar	10 clinvar	4 clinvar	153
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	145	11	8	164

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007086.4	RefSeq	NP_009017.1	25	MANE Select
ENST00000360586.8	Ensembl	ENSP00000353793.3	25	MANE Select
NM_001008396.3	RefSeq	NP_001008397.1	22	Standard
ENST00000420358.2	Ensembl	ENSP00000399349.2	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mesodermal Commitment Pathway

Biological Process

mitotic cell cycle
DNA-dependent DNA replication
DNA repair
regulation of transcription by RNA polymerase II
cellular response to DNA damage stimulus

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
chromatin binding
protein binding

Cellular Component

nucleoplasm
cytoplasm
replication fork protection complex
nuclear replication fork

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000360586
Coding exons: 25
Length: 88156
Individuals with no LoFs: 125490
Homozygous LoFs: 0
Heterozygous LoFs: 258
Defined: 125748
p: 0.00103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.137	594	585	1.02	0.0000288	7448
Missense (PolyPhen)		142	162.95	0.87145		1966
Synonymous	0.903	180	196	0.918	0.00000979	2062
Loss of Function	2.85	38	62.2	0.610	0.00000339	744

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00075	0.00074	rare
Latino/Admixed American	0.00088	0.00081	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00066	0.00060	rare
Finnish	0.0025	0.0024	notable
European (Non-Finnish)	0.00080	0.00077	rare
South Asian	0.0021	0.0021	notable
Other	0.00038	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a replication initiation factor that brings together the MCM2-7 helicase and the DNA polymerase alpha/primase complex in order to initiate DNA replication. {ECO:0000269|PubMed:19805216}.;

Recessive Scores

pRec: 0.0916

Intolerance Scores

LoFtool: 0.959
RVIS EVS: 0.79
RVIS percentile EVS: 87.29

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.789

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium