GRWD1

protein-coding

glutamate rich WD repeat containing 1, the group of WD repeat domain containing

Gene summary

This gene encodes a glutamate-rich protein that contains five WD-repeat motifs. The encoded protein may play a critical role in ribosome biogenesis and may also play a role in histone methylation through interactions with CUL4-DDB1 ubiquitin E3 ligase. [provided by RefSeq, Feb 2012]

MANE transcript

NM_031485.4

Inheritance

ClinVar variants

P:2U:94B:11

Top phenotype

GRWD1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.44

Max pathogenic AF

—

Genomic locus

chr19:48,445,841-48,457,022

External References & Databases

Ensembl (ENSG00000105447)

Transcript & Mutation Effects

hg38 • Region Span ~11.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital diarrheaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0000824

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GRWD1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 93

GRWD1-related disorderTotal: 12

Diarrhea 14, congenitalTotal: 2

Congenital diarrheaTotal: 2

not providedTotal: 1

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031485.4. 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	9 clinvar		11
missense		2 clinvar	92 clinvar	1 clinvar	1 clinvar	96
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	2	94	10	1	107

Highest pathogenic variant AF is 0.0002453474

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031485.4	RefSeq	NP_113673.3	7	MANE Select
ENST00000253237.10	Ensembl	ENSP00000253237.4	7	MANE Select
ENST00000598711.1	Ensembl	ENSP00000468943.1	4	Standard
ENST00000928855.1	Ensembl	ENSP00000598914.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

DNA replication
nucleosome assembly
nucleosome disassembly

Molecular Function

chromatin binding
DNA replication origin binding
RNA binding
protein binding
histone binding

Cellular Component

nucleus
chromosome
nucleolus
cytosol
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000253237
Coding exons: 7
Length: 11250
Individuals with no LoFs: 125628
Homozygous LoFs: 0
Heterozygous LoFs: 120
Defined: 125748
p: 0.000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.104	282	287	0.983	0.0000180	2853
Missense (PolyPhen)		86	96.583	0.89043		1009
Synonymous	0.0874	124	125	0.990	0.00000830	920
Loss of Function	2.33	9	20.3	0.443	9.63e-7	206

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.0026	0.0026	notable
East Asian	0.0011	0.0011	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00051	0.00051	rare
South Asian	0.000033	0.000033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Histone binding-protein that regulates chromatin dynamics and minichromosome maintenance (MCM) loading at replication origins, possibly by promoting chromatin openness (PubMed:25990725). {ECO:0000269|PubMed:25990725}.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.692
RVIS EVS: -0.38
RVIS percentile EVS: 28.01

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.962

Gene Damage Prediction

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