GAS2

protein-coding

growth arrest specific 2

Gene summary

The protein encoded by this gene is a caspase-3 substrate that plays a role in regulating microfilament and cell shape changes during apoptosis. It can also modulate cell susceptibility to p53-dependent apoptosis by inhibiting calpain activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2017]

MANE transcript

NM_001143830.3

Inheritance

AR, AD

ClinVar variants

P:2U:34B:1

Top phenotype

Deafness, autosomal recessive, 25

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr11:22,625,509-22,813,001

External References & Databases

Ensembl (ENSG00000148935)

Transcript & Mutation Effects

hg38 • Region Span ~187.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hearing loss, autosomal recessive 125MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0971152

Submitter: PanelApp Australia

hearing loss, autosomal recessive 125LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0971152

Submitter: Ambry Genetics

hearing loss disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005365

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Deafness, autosomal recessive, 25AR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 33964205

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GAS2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 31

Hearing loss, autosomal recessive 125Total: 2

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001143830.3. 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			1 clinvar		1 clinvar	2
missense		1 clinvar	31 clinvar			32
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar		2 clinvar			3
Total	1	1	34	0	1	37

Highest pathogenic variant AF is 6.936429e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001143830.3	RefSeq	NP_001137302.1	7	MANE Select
ENST00000454584.7	Ensembl	ENSP00000401145.2	7	MANE Select
NM_001351224.3	RefSeq	NP_001338153.1	7	Standard
NM_001391933.1	RefSeq	NP_001378862.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

induction of apoptosis through dr3 and dr4/5 death receptors
Caspase-mediated cleavage of cytoskeletal proteins
Apoptotic cleavage of cellular proteins
Apoptotic execution phase
Apoptosis

Biological Process

initiation of primordial ovarian follicle growth
antral ovarian follicle growth
apoptotic process
cell cycle arrest
regulation of cell shape

Molecular Function

microtubule binding

Cellular Component

cytosol
actin filament
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000454584
Coding exons: 7
Length: 187414
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125747
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.440	154	170	0.905	0.00000876	2039
Missense (PolyPhen)		39	56.149	0.69457		641
Synonymous	0.161	60	61.6	0.974	0.00000312	599
Loss of Function	2.15	8	17.8	0.449	0.00000110	201

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in apoptosis by acting as a cell death substrate for caspases. Is cleaved during apoptosis and the cleaved form induces dramatic rearrangements of the actin cytoskeleton and potent changes in the shape of the affected cells. May be involved in the membrane ruffling process (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.724
RVIS EVS: 0.19
RVIS percentile EVS: 66.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.845

Gene Damage Prediction

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