ARHGAP31

protein-coding

Rho GTPase activating protein 31, the group of Rho GTPase activating proteins

Gene summary

This gene encodes a GTPase-activating protein (GAP). A variety of cellular processes are regulated by Rho GTPases which cycle between an inactive form bound to GDP and an active form bound to GTP. This cycling between inactive and active forms is regulated by guanine nucleotide exchange factors and GAPs. The encoded protein is a GAP shown to regulate two GTPases involved in protein trafficking and cell growth. [provided by RefSeq, Jul 2008]

MANE transcript

NM_020754.4

Inheritance

ClinVar variants

P:5U:390B:203

Top phenotype

Adams-Oliver syndrome 1

gnomAD constraint

pLI —, LoF o/e 0.09

Max pathogenic AF

—

Genomic locus

chr3:119,294,383-119,420,714

External References & Databases

Ensembl (ENSG00000031081)

Transcript & Mutation Effects

hg38 • Region Span ~126.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Adams-Oliver syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007034

Submitter: Orphanet

Adams-Oliver syndrome 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024506

Submitter: G2P

Adams-Oliver syndrome 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024506

Submitter: Labcorp Genetics (formerly Invitae)

Adams-Oliver syndrome 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0024506

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Adams-Oliver syndrome 1AD

Manifestation: Craniofacial; Dermatologic; Musculoskeletal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 474617; 16451141; 19610107; 21565291

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ARHGAP31 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 445

Inborn genetic diseasesTotal: 193

not specifiedTotal: 99

ARHGAP31-related disorderTotal: 86

Adams-Oliver syndrome 1Total: 56

Intellectual disabilityTotal: 2

Cerebral palsyTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020754.4. 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			5 clinvar	111 clinvar	8 clinvar	124
missense			361 clinvar	79 clinvar	5 clinvar	445
nonsense	2 clinvar	1 clinvar	13 clinvar			16
start loss						0
frameshift	1 clinvar	1 clinvar	10 clinvar			12
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	3	2	390	190	13	598

Highest pathogenic variant AF is 6.84046e-7

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_020754.4	RefSeq	NP_065805.2	12	MANE Select
ENST00000264245.9	Ensembl	ENSP00000264245.4	12	MANE Select
ENST00000482743.1	Ensembl	ENSP00000418429.1	6	Standard
ENST00000861944.1	Ensembl	ENSP00000532003.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
Rho GTPase cycle
Signaling by Rho GTPases

Biological Process

small GTPase mediated signal transduction
positive regulation of GTPase activity
regulation of small GTPase mediated signal transduction

Molecular Function

GTPase activator activity
SH3 domain binding

Cellular Component

cytosol
focal adhesion
lamellipodium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264245
Coding exons: 12
Length: 126342
Individuals with no LoFs: 124782
Homozygous LoFs: 0
Heterozygous LoFs: 18
Defined: 124800
p: 0.0000721

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.797	706	768	0.919	0.0000433	9360
Missense (PolyPhen)		243	300.7	0.8081		3663
Synonymous	0.997	291	313	0.928	0.0000192	2992
Loss of Function	6.23	5	54.8	0.0912	0.00000301	653

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as a GTPase-activating protein (GAP) for RAC1 and CDC42. Required for cell spreading, polarized lamellipodia formation and cell migration. {ECO:0000269|PubMed:12192056, ECO:0000269|PubMed:16519628}.;
Disease: DISEASE: Adams-Oliver syndrome 1 (AOS1) [MIM:100300]: A disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse limb defects, syndactyly, most commonly of second and third toes, can also be observed. The clinical features are highly variable and can also include cardiovascular malformations, brain abnormalities and vascular defects such as cutis marmorata and dilated scalp veins. {ECO:0000269|PubMed:21565291}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.239
RVIS EVS: 0.59
RVIS percentile EVS: 82.35

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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