SRGAP1

SLIT-ROBO Rho GTPase activating protein 1, the group of AH/BAR family Rho GTPase activating proteins|F-BAR domain containing

Basic information

Region (hg38): 12:63843760-64162217

Links

ENSG00000196935 ∙ NCBI:57522 ∙ OMIM:606523 ∙ HGNC:17382 ∙ Uniprot:Q7Z6B7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thyroid cancer, nonmedullary, 2 (No Known Disease Relationship), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SRGAP1 gene.

• not provided (27 variants)
• Inborn genetic diseases (27 variants)
• Thyroid cancer, nonmedullary, 2 (2 variants)
• SRGAP1-related condition (2 variants)
• Congenital anomaly of kidney and urinary tract (2 variants)
• not specified (1 variants)
• Nephronophthisis (1 variants)
• Congenital anomalies of kidney and urinary tract 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SRGAP1 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				8	7	15
missense			33	2	1	36
nonsense						0
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				3	1	4
non coding				1	2	3
Total	0	0	35	11	10

Variants in SRGAP1

This is a list of pathogenic ClinVar variants found in the SRGAP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-63844892-G-A			Likely benign (Apr 09, 2018)
12-63984024-C-T			Benign/Likely benign (Jun 01, 2022)
12-63984040-G-A		SRGAP1-related disorder	Uncertain significance (Oct 23, 2023)
12-63984061-C-T		Thyroid cancer, nonmedullary, 2 • not specified	Uncertain significance (Mar 04, 2024)
12-63984062-G-A			Likely benign (Jun 08, 2018)
12-63984086-G-C		not specified	Uncertain significance (Nov 30, 2022)
12-63984101-C-A		not specified	Uncertain significance (Dec 16, 2023)
12-64016946-A-T		SRGAP1-related disorder	Likely benign (Apr 08, 2019)
12-64016970-A-C		Thyroid cancer, nonmedullary, 2	Pathogenic (May 01, 2013)
12-64016975-A-T		not specified	Uncertain significance (Oct 10, 2023)
12-64017011-C-T		not specified	Uncertain significance (Dec 14, 2023)
12-64042855-C-T		SRGAP1-related disorder	Likely benign (Mar 02, 2021)
12-64042931-C-T		Inborn genetic diseases	Uncertain significance (Nov 16, 2021)
12-64043443-C-G			Benign (Dec 31, 2019)
12-64043493-G-A		not specified	Uncertain significance (Jan 24, 2024)
12-64043505-T-TAG		Thyroid cancer, nonmedullary, 2	Uncertain significance (Feb 19, 2020)
12-64043534-G-A			Uncertain significance (Aug 01, 2022)
12-64062920-TG-GT		SRGAP1-related disorder	Uncertain significance (Nov 17, 2022)
12-64062921-G-A		Congenital anomaly of kidney and urinary tract • Nephronophthisis	Uncertain significance (May 28, 2020)
12-64062938-G-A		Thyroid cancer, nonmedullary, 2	Pathogenic (May 01, 2013)
12-64062966-A-G		not specified	Uncertain significance (Aug 02, 2023)
12-64063055-G-A		not specified	Uncertain significance (Mar 22, 2022)
12-64063167-G-A			Benign (Mar 01, 2022)
12-64065207-C-T		SRGAP1-related disorder	Benign (Dec 31, 2019)
12-64078911-A-G			Likely benign (Jul 18, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SRGAP1	protein_coding	protein_coding	ENST00000355086	22	303541

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00155	125729	0	17	125746	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.21	454	607	0.748	0.0000330	7204
Missense in Polyphen		90	150.86	0.59656		1767
Synonymous	1.39	202	229	0.883	0.0000130	2019
Loss of Function	5.81	8	54.1	0.148	0.00000293	654

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000110	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000719	0.0000703
Middle Eastern	0.000110	0.000109
South Asian	0.000131	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: GTPase-activating protein for RhoA and Cdc42 small GTPases. Together with CDC42 seems to be involved in the pathway mediating the repulsive signaling of Robo and Slit proteins in neuronal migration. SLIT2, probably through interaction with ROBO1, increases the interaction of SRGAP1 with ROBO1 and inactivates CDC42. {ECO:0000269|PubMed:11672528}.
• Disease: DISEASE: Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470]: A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. {ECO:0000269|PubMed:23539728}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Axon guidance - Homo sapiens (human);Developmental Biology;Signal Transduction;Rho GTPase cycle;Inactivation of CDC42 and RAC1;Signaling by Rho GTPases;Signaling by ROBO receptors;Axon guidance;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.136

Intolerance Scores

• loftool: 0.610
• rvis_EVS: -0.82
• rvis_percentile_EVS: 12.01

Haploinsufficiency Scores

• pHI: 0.370
• hipred: Y
• hipred_score: 0.756
• ghis: 0.548

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.503

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Srgap1

Gene ontology

• Biological process: signal transduction;negative regulation of cell migration;positive regulation of GTPase activity;regulation of small GTPase mediated signal transduction
• Cellular component: cytoplasm;cytosol
• Molecular function: GTPase activator activity;protein binding;Rac GTPase binding