ARHGAP31

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

Basic information

Region (hg38): 3:119294383-119420714

Links

ENSG00000031081 ∙ NCBI:57514 ∙ OMIM:610911 ∙ HGNC:29216 ∙ Uniprot:Q2M1Z3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Adams-Oliver syndrome 1 (Strong), mode of inheritance: AD
• Adams-Oliver syndrome (Supportive), mode of inheritance: AD
• Adams-Oliver syndrome 1 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Adams-Oliver syndrome 1	AD	General	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	Craniofacial; Dermatologic; Musculoskeletal	474617; 16451141; 19610107; 21565291

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARHGAP31 gene.

• not_provided (378 variants)
• Inborn_genetic_diseases (166 variants)
• ARHGAP31-related_disorder (58 variants)
• Adams-Oliver_syndrome_1 (53 variants)
• not_specified (32 variants)
• Adams-Oliver_syndrome (2 variants)
• Intellectual_disability (2 variants)
• Cerebral_palsy (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARHGAP31 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020754.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	83	10	97
missense			307	61	7	375
nonsense	2		6			8
start loss						0
frameshift	1	1	7			9
splice donor/acceptor (+/-2bp)			1			1
Total	3	1	325	144	17

Highest pathogenic variant AF is 6.84046e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARHGAP31	protein_coding	protein_coding	ENST00000264245	12	126342

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000852	124782	0	18	124800	0.0000721

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.797	706	768	0.919	0.0000433	9360
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000115	0.000106
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

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.
• Pathway: Signal Transduction;Rho GTPase cycle;Signaling by Rho GTPases (Consensus)

Intolerance Scores

• loftool: 0.239
• rvis_EVS: 0.59
• rvis_percentile_EVS: 82.35

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.658
• ghis: 0.455

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Arhgap31

Gene ontology

• Biological process: small GTPase mediated signal transduction;positive regulation of GTPase activity;regulation of small GTPase mediated signal transduction
• Cellular component: cytosol;focal adhesion;lamellipodium
• Molecular function: GTPase activator activity;SH3 domain binding