SASH1

SAM and SH3 domain containing 1, the group of SAM and SH3 domain containing|Sterile alpha motif domain containing

Basic information

Region (hg38): 6:148272304-148552044

Links

ENSG00000111961 ∙ NCBI:23328 ∙ OMIM:607955 ∙ HGNC:19182 ∙ Uniprot:O94885 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial generalized lentiginosis (Supportive), mode of inheritance: AD
• pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome (Supportive), mode of inheritance: AR
• pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome (Limited), mode of inheritance: AR
• dyschromatosis universalis hereditaria 1 (Limited), mode of inheritance: AD
• pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma	AR	Oncologic	The condition can involve the development of squamous cell carcinomas, and awareness may allow surveilance in order to allow prompt diagnosis and management	Dental; Dermatologic; Oncologic	25315659; 26203640; 27659786; 27840890; 28407215; 29956681

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SASH1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SASH1 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				19	5	24
missense		9	95	9	3	116
nonsense						0
start loss						0
frameshift			1			1
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region				8	4	12
non coding			1	1	35	37
Total	0	9	97	29	44

Variants in SASH1

This is a list of pathogenic ClinVar variants found in the SASH1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-148343099-C-T		Inborn genetic diseases	Uncertain significance (Apr 22, 2022)
6-148343106-T-TGAGCCC		Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma;Dyschromatosis universalis hereditaria 1	Benign (Jul 20, 2021)
6-148343146-C-G		Inborn genetic diseases	Uncertain significance (Sep 01, 2021)
6-148343147-C-G		Inborn genetic diseases	Uncertain significance (Dec 06, 2021)
6-148343170-G-C		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
6-148343178-A-G		SASH1-related disorder	Likely benign (Mar 01, 2019)
6-148343182-G-A		Inborn genetic diseases	Uncertain significance (Dec 31, 2023)
6-148343215-G-C		Inborn genetic diseases	Uncertain significance (Oct 25, 2023)
6-148343268-G-A			Benign (May 15, 2021)
6-148390136-C-T			Likely benign (Sep 27, 2018)
6-148390137-G-A		Inborn genetic diseases	Uncertain significance (Dec 13, 2023)
6-148390158-G-A		Inborn genetic diseases	Uncertain significance (Dec 27, 2022)
6-148390171-A-G		Inborn genetic diseases	Uncertain significance (Jan 03, 2022)
6-148390206-G-T		Inborn genetic diseases	Uncertain significance (Oct 10, 2023)
6-148390208-G-A			Likely benign (Apr 02, 2018)
6-148390235-A-G		SASH1-related disorder	Likely benign (Apr 01, 2023)
6-148390236-C-T		Inborn genetic diseases	Uncertain significance (Mar 25, 2024)
6-148390546-A-G			Benign (Nov 12, 2018)
6-148439903-G-A			Benign (Jun 19, 2021)
6-148439903-G-T			Benign (Nov 12, 2018)
6-148440206-C-T		Inborn genetic diseases	Uncertain significance (Feb 26, 2024)
6-148440221-G-A		Inborn genetic diseases	Uncertain significance (Jun 11, 2021)
6-148440226-C-G			Benign (Dec 31, 2019)
6-148440227-A-C		Inborn genetic diseases	Uncertain significance (Dec 31, 2023)
6-148440320-G-C		Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma • Dyschromatosis universalis hereditaria 1	Benign (Nov 07, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SASH1	protein_coding	protein_coding	ENST00000367467	20	279747

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00180	0.998	125700	0	48	125748	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.604	701	747	0.938	0.0000463	8082
Missense in Polyphen		252	314.69	0.80079		3414
Synonymous	-0.505	327	316	1.04	0.0000219	2512
Loss of Function	4.89	16	55.2	0.290	0.00000289	688

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000756	0.000750
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000337	0.000326
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000160	0.000158
Middle Eastern	0.000337	0.000326
South Asian	0.000136	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May have a role in a signaling pathway. Could act as a tumor suppressor.

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.521
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.07

Haploinsufficiency Scores

• pHI: 0.369
• hipred: N
• hipred_score: 0.492
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.867

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sash1

Gene ontology

• Biological process: protein polyubiquitination;positive regulation of endothelial cell migration;positive regulation of lipopolysaccharide-mediated signaling pathway;positive regulation of JUN kinase activity;positive regulation of angiogenesis;regulation of protein K63-linked ubiquitination;positive regulation of p38MAPK cascade;positive regulation of NIK/NF-kappaB signaling;regulation of protein autoubiquitination
• Cellular component: protein-containing complex
• Molecular function: protein C-terminus binding;protein kinase binding;mitogen-activated protein kinase kinase kinase binding;protein-containing complex scaffold activity