SAV1

salvador family WW domain containing protein 1

Basic information

Region (hg38): 14:50632058-50668306

Links

ENSG00000151748 ∙ NCBI:60485 ∙ OMIM:607203 ∙ HGNC:17795 ∙ Uniprot:Q9H4B6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SAV1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SAV1 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						0
missense			17	1		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			28	9	7	44
Total	0	0	45	10	7

Variants in SAV1

This is a list of pathogenic ClinVar variants found in the SAV1 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-50632151-A-G			Likely benign (Aug 14, 2018)
14-50632152-C-A			Benign (Jun 16, 2018)
14-50632211-T-C		Hereditary spastic paraplegia 3A	Likely benign (Jul 01, 2021)
14-50632215-T-C		Hereditary spastic paraplegia 3A	Uncertain significance (Jan 12, 2018)
14-50632216-GC-G		Hereditary spastic paraplegia 3A	Likely benign (Jan 07, 2024)
14-50632234-G-C		Inborn genetic diseases • Hereditary spastic paraplegia 3A	Uncertain significance (Feb 22, 2023)
14-50632235-T-C		Hereditary spastic paraplegia 3A	Uncertain significance (Jun 04, 2022)
14-50632236-A-G		Hereditary spastic paraplegia 3A • Inborn genetic diseases	Uncertain significance (Jan 19, 2024)
14-50632264-C-A		Hereditary spastic paraplegia 3A	Uncertain significance (Apr 06, 2023)
14-50632273-G-C		Hereditary spastic paraplegia 3A	Likely benign (Jul 18, 2023)
14-50632274-T-A		Inborn genetic diseases • Hereditary spastic paraplegia 3A	Uncertain significance (Aug 30, 2023)
14-50632274-TATC-T		Inborn genetic diseases	Uncertain significance (Nov 20, 2023)
14-50632278-A-C		Inborn genetic diseases	Uncertain significance (Mar 31, 2024)
14-50632285-T-G		Hereditary spastic paraplegia 3A • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 22, 2024)
14-50632293-C-T		Hereditary spastic paraplegia 3A	Uncertain significance (Feb 07, 2022)
14-50632296-C-T		Neuropathy, hereditary sensory, type 1D	Uncertain significance (Aug 29, 2019)
14-50632297-A-G		Hereditary spastic paraplegia 3A • Neuropathy, hereditary sensory, type 1D	Benign (Oct 14, 2023)
14-50632300-G-C		Hereditary spastic paraplegia 3A	Uncertain significance (Apr 02, 2021)
14-50632301-T-G		Hereditary spastic paraplegia 3A	Uncertain significance (Dec 29, 2021)
14-50632302-C-T		Hereditary spastic paraplegia 3A	Uncertain significance (Aug 12, 2021)
14-50632303-G-A		Hereditary spastic paraplegia 3A • Inborn genetic diseases	Likely benign (Apr 18, 2022)
14-50632312-T-A		Hereditary spastic paraplegia 3A	Likely benign (Jul 17, 2023)
14-50632313-G-T			Uncertain significance (Jul 15, 2016)
14-50632325-A-G		Hereditary spastic paraplegia 3A	Uncertain significance (Sep 07, 2021)
14-50632327-G-T		Hereditary spastic paraplegia 3A	Uncertain significance (Jul 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SAV1	protein_coding	protein_coding	ENST00000324679	5	36274

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000904	0.997	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.684	232	204	1.13	0.0000100	2477
Missense in Polyphen		59	62.649	0.94176		740
Synonymous	-0.107	73	71.8	1.02	0.00000340	738
Loss of Function	2.64	9	22.5	0.400	0.00000150	230

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000127	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000984	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulator of STK3/MST2 and STK4/MST1 in the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. SAV1 is required for STK3/MST2 and STK4/MST1 activation and promotes cell-cycle exit and terminal differentiation in developing epithelial tissues. Plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, and its ability to phosphorylate CROCC and CEP250. In conjunction with STK3/MST2, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. {ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:19212654, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:21104395}.
• Pathway: Hippo signaling pathway - Homo sapiens (human);Hippo signaling pathway - multiple species - Homo sapiens (human);Signal Transduction;Signaling by Hippo (Consensus)

Recessive Scores

• pRec: 0.228

Intolerance Scores

• loftool: 0.707
• rvis_EVS: -0.29
• rvis_percentile_EVS: 32.94

Haploinsufficiency Scores

• pHI: 0.649
• hipred: Y
• hipred_score: 0.776
• ghis: 0.580

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.849

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sav1
• Phenotype: vision/eye phenotype; digestive/alimentary phenotype; respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; neoplasm; 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); 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); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: sav1
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: increased curvature

Gene ontology

• Biological process: hair follicle development;apoptotic process;signal transduction;keratinocyte differentiation;hippo signaling;positive regulation of fat cell differentiation;negative regulation of epithelial cell proliferation;protein stabilization;positive regulation of DNA-binding transcription factor activity;negative regulation of cardiac muscle cell proliferation;ventricular septum morphogenesis;lung epithelial cell differentiation;intestinal epithelial cell differentiation;regulation of stem cell population maintenance
• Cellular component: nucleus;cytoplasm;cytosol
• Molecular function: protein binding;protein-containing complex scaffold activity;identical protein binding