WDR91

protein-coding

WD repeat domain 91, the group of WD repeat domain containing|MicroRNA protein coding host genes

Gene summary

Enables phosphatidylinositol 3-kinase inhibitor activity. Involved in early endosome to late endosome transport and regulation of protein catabolic process. Located in cytosol; early endosome membrane; and late endosome membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_014149.4

Inheritance

ClinVar variants

P:4U:118B:10

Top phenotype

complex neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr7:135,183,839-135,211,555

External References & Databases

Ensembl (ENSG00000105875)

Transcript & Mutation Effects

hg38 • Region Span ~27.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: LiferaOmics

Genetic evidence – Published PMID: 34791078 – Family 1 – one affected individual. Case-level (AR homozygous canonical splice; predicted null; default = 1.5; consanguineous cohort context; −0.5 consanguinity deduction applied) = 1.0; Segregation = 0; Case-control = 0 PMID: 40550703 – Family 1 – one affected neonate. Case-level (AR homozygous canonical splice; predicted null; default = 1.5; consanguineous family; −0.5 consanguinity deduction applied) = 1.0; Segregation = 0; Case-control = 0 PMID: 32732226 – Family 1 – one affected fetus. Case-level (AR homozygous nonsense; predicted null; default = 1.5; no consanguinity information provided; no deduction applied) = 1.5; Segregation = 0; Case-control = 0 Published genetic evidence total = 3.5 Genetic evidence – Our case Family 1 – one proband. Case-level (AR homozygous missense; non-LOF start = 0.1; consanguineous family) = 0.1; Segregation = 0; Case-control = 0 Our case genetic evidence total = 0.1 Total genetic evidence (Published + Our case) 3.6 / 12 Experimental evidence – Published (conservative) PMID: 28860274 – Animal model (brain-specific Wdr91 inactivation impairing brain development). Model system (phenotype-aligned abnormal brain development; conservative scoring) = 1.0 PMID: 40225931 – Splice variant functional validation (minigene assay showing exon skipping for c.1395+1G>A). Functional alteration (engineered system; confirms LoF mechanism; conservative scoring) = 0.5 Experimental evidence total = 1.5 / 6 Overall score Genetic evidence = 3.6 Experimental evidence = 1.5 Total = 5.1

complex neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to WDR91 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 107

not providedTotal: 11

Neurodevelopmental disorder with brain malformations and multiple congenital anomaliesTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014149.4. 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			6 clinvar	1 clinvar	2 clinvar	9
missense			106 clinvar	7 clinvar		113
nonsense	1 clinvar	1 clinvar	2 clinvar			4
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	1 clinvar			3
Total	2	2	118	8	2	132

Highest pathogenic variant AF is 0.00008686361

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014149.4	RefSeq	NP_054868.3	15	MANE Select
ENST00000354475.5	Ensembl	ENSP00000346466.4	15	MANE Select
NM_001362736.2	RefSeq	NP_001349665.1	16	Standard
NM_001362737.2	RefSeq	NP_001349666.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ubiquitin-dependent protein catabolic process
regulation of phosphatidylinositol 3-kinase activity
early endosome to late endosome transport
regulation of cellular protein catabolic process

Molecular Function

protein binding
phosphatidylinositol 3-kinase regulator activity

Cellular Component

cytosol
extrinsic component of endosome membrane
early endosome membrane
late endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000354475
Coding exons: 15
Length: 27727
Individuals with no LoFs: 125700
Homozygous LoFs: 0
Heterozygous LoFs: 48
Defined: 125748
p: 0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.43	358	443	0.809	0.0000258	4873
Missense (PolyPhen)		73	128.89	0.56639		1394
Synonymous	0.103	190	192	0.991	0.0000124	1476
Loss of Function	3.42	16	39.1	0.409	0.00000206	429

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport (PubMed:26783301). It is for instance, required for the delivery of cargos like BST2/tetherin from early to late endosome and thereby participates indirectly to their degradation by the lysosome (PubMed:27126989). May play a role in meiosis (By similarity). {ECO:0000250|UniProtKB:Q7TMQ7, ECO:0000269|PubMed:26783301, ECO:0000269|PubMed:27126989}.;

Recessive Scores

pRec: 0.0934

Intolerance Scores

LoFtool: 0.414
RVIS EVS: -1.28
RVIS percentile EVS: 5.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.435

Gene Damage Prediction

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