GAS1

growth arrest specific 1

Basic information

Region (hg38): 9:86944362-86947506

Links

ENSG00000180447 ∙ NCBI:2619 ∙ OMIM:139185 ∙ HGNC:4165 ∙ Uniprot:P54826 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• holoprosencephaly (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Holoprosencephaly 4	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; Endocrine; Neurologic	20583177; 21842183
Individuals with holoprosencephaly may demonstrate endocrine anomalies, including diabetes insipidus

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GAS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GAS1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				26	2	28
missense			34	3	1	38
nonsense						0
start loss						0
frameshift						0
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1	6	7
Total	0	0	37	30	9

Variants in GAS1

This is a list of pathogenic ClinVar variants found in the GAS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-86945528-C-G			Benign (Dec 22, 2018)
9-86945534-G-A			Benign (Apr 12, 2019)
9-86945748-G-C			Likely benign (Jun 04, 2022)
9-86945749-A-T			Uncertain significance (Mar 26, 2022)
9-86945774-T-G		not specified	Uncertain significance (Aug 11, 2024)
9-86945777-A-T		not specified	Uncertain significance (Jan 23, 2023)
9-86945780-C-T		not specified	Uncertain significance (Oct 01, 2024)
9-86945787-G-A			Likely benign (Jul 17, 2023)
9-86945787-G-C			Benign (Jul 30, 2018)
9-86945804-G-A			Uncertain significance (Sep 27, 2022)
9-86945813-G-GGCC			Uncertain significance (Sep 15, 2022)
9-86945822-C-A			Likely benign (Dec 12, 2023)
9-86945828-T-C			Likely benign (Nov 28, 2022)
9-86945836-C-T		not specified	Uncertain significance (Aug 19, 2024)
9-86945838-C-A			Likely benign (Dec 09, 2021)
9-86945848-T-C			Uncertain significance (Nov 18, 2023)
9-86945852-G-A			Likely benign (Sep 15, 2023)
9-86945853-C-A			Likely benign (Oct 24, 2023)
9-86945865-G-A			Likely benign (Aug 01, 2022)
9-86945872-G-A		not specified	Uncertain significance (Apr 15, 2024)
9-86945886-G-A		GAS1-related disorder	Likely benign (Sep 27, 2023)
9-86945915-C-G			Uncertain significance (Nov 17, 2022)
9-86945929-A-G		not specified	Uncertain significance (May 13, 2024)
9-86945938-T-C			Uncertain significance (Nov 27, 2023)
9-86945969-C-T		not specified	Uncertain significance (Nov 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GAS1	protein_coding	protein_coding	ENST00000298743	1	2826

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.819	0.177	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.747	110	134	0.819	0.00000633	2126
Missense in Polyphen		28	48.425	0.57821		690
Synonymous	-3.42	95	61.1	1.56	0.00000309	758
Loss of Function	2.20	0	5.65	0.00	2.45e-7	84

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Specific growth arrest protein involved in growth suppression. Blocks entry to S phase. Prevents cycling of normal and transformed cells. {ECO:0000269|PubMed:8127893}.
• Pathway: Hedgehog signaling pathway - Homo sapiens (human);HH-Ncore;Hedgehog Signaling Pathway;Signal Transduction;Ligand-receptor interactions;Hedgehog ,on, state;Signaling by Hedgehog;FOXM1 transcription factor network;Signaling events mediated by the Hedgehog family (Consensus)

Haploinsufficiency Scores

• pHI: 0.478
• hipred: N
• hipred_score: 0.358
• ghis: 0.640

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gas1
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; pigmentation phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; skeleton phenotype; vision/eye phenotype

Gene ontology

• Biological process: cell cycle arrest;regulation of smoothened signaling pathway;negative regulation of protein processing;cellular response to vascular endothelial growth factor stimulus;regulation of apoptotic process;cell fate commitment;negative regulation of mitotic cell cycle;developmental growth;regulation of ER to Golgi vesicle-mediated transport
• Cellular component: plasma membrane;integral component of membrane;anchored component of plasma membrane
• Molecular function: protein binding