SEPTIN12

septin 12, the group of Septins

Basic information

Region (hg38): 16:4777606-4788398

Previous symbols: [ "SEPT12" ]

Links

ENSG00000140623 ∙ NCBI:124404 ∙ OMIM:611562 ∙ HGNC:26348 ∙ Uniprot:Q8IYM1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-syndromic male infertility due to sperm motility disorder (Supportive), mode of inheritance: AR
• spermatogenic failure 10 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 10	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	Genitourinary	22275165; 22479503

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SEPTIN12 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SEPTIN12 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				2	2	4
missense			43	2		45
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					13	13
Total	0	0	43	4	15

Variants in SEPTIN12

This is a list of pathogenic ClinVar variants found in the SEPTIN12 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-4777826-C-T		not specified	Uncertain significance (Oct 26, 2022)
16-4777828-C-T		not specified	Uncertain significance (Sep 26, 2024)
16-4777850-G-A		not specified	Uncertain significance (Dec 28, 2023)
16-4777867-C-T		not specified	Uncertain significance (Jun 06, 2023)
16-4777876-G-T		not specified	Uncertain significance (Dec 04, 2024)
16-4777879-G-A		not specified	Uncertain significance (May 28, 2024)
16-4777892-C-T		not specified	Uncertain significance (Jan 16, 2024)
16-4777901-G-T		not specified	Uncertain significance (Oct 08, 2024)
16-4777919-G-C		not specified	Uncertain significance (Jul 12, 2023)
16-4777942-C-T		not specified	Uncertain significance (Apr 11, 2023)
16-4777943-G-A		not specified	Uncertain significance (Nov 12, 2021)
16-4777960-A-G		not specified	Uncertain significance (Dec 06, 2021)
16-4777967-G-C		not specified	Uncertain significance (May 28, 2024)
16-4777969-G-A		Spermatogenic failure 10	Uncertain significance (Apr 04, 2024)
16-4777973-T-C		not specified	Uncertain significance (Aug 16, 2021)
16-4778101-C-G		not specified	Uncertain significance (Mar 20, 2023)
16-4778122-T-C		not specified	Uncertain significance (Mar 30, 2024)
16-4779691-T-A		not specified	Uncertain significance (Sep 20, 2024)
16-4779695-A-G			Likely benign (Sep 01, 2024)
16-4779725-A-T		not specified	Uncertain significance (Jan 03, 2024)
16-4779735-C-T		not specified	Uncertain significance (Dec 08, 2023)
16-4779736-G-A			Likely benign (Nov 01, 2024)
16-4779768-C-T			Uncertain significance (Jan 01, 2023)
16-4779769-G-A		SEPTIN12-related disorder	Likely benign (Feb 21, 2019)
16-4780067-G-C			Benign (Nov 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SEPTIN12	protein_coding	protein_coding	ENST00000268231	9	10853

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.35e-19	0.000175	125559	0	189	125748	0.000752

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.54	292	227	1.29	0.0000145	2339
Missense in Polyphen		131	109.81	1.193		1091
Synonymous	-4.65	155	96.8	1.60	0.00000661	701
Loss of Function	-1.64	24	16.8	1.43	8.02e-7	179

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000992	0.000911
Ashkenazi Jewish	0.00726	0.00727
East Asian	0.000602	0.000598
Finnish	0.0000929	0.0000924
European (Non-Finnish)	0.000309	0.000308
Middle Eastern	0.000602	0.000598
South Asian	0.00144	0.00144
Other	0.000824	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Filament-forming cytoskeletal GTPase (By similarity). Involved in spermatogenesis. Involved in the morphogenesis of sperm heads and the elongation of sperm tails probably implicating the association with alpha- and beta-tubulins (PubMed:24213608). Forms a filamentous structure with SEPT7, SEPT6, SEPT2 and probably SEPT4 at the sperm annulus which is required for the structural integrity and motility of the sperm tail during postmeiotic differentiation (PubMed:25588830). May play a role in cytokinesis (Potential). {ECO:0000250, ECO:0000269|PubMed:24213608, ECO:0000269|PubMed:25588830, ECO:0000305}.
• Disease: DISEASE: Spermatogenic failure 10 (SPGF10) [MIM:614822]: An infertility disorder caused by spermatogenesis defects. It results in decreased sperm motility, concentration, and multiple sperm structural defects. The most prominent feature is a defective sperm annulus, a ring structure that demarcates the midpiece and the principal piece of the sperm tail. {ECO:0000269|PubMed:22275165, ECO:0000269|PubMed:25588830, ECO:0000269|PubMed:25775403}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Bacterial invasion of epithelial cells - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.805
• rvis_EVS: -0.38
• rvis_percentile_EVS: 28.01

Haploinsufficiency Scores

• pHI: 0.221
• hipred: N
• hipred_score: 0.219
• ghis: 0.450

Essentials

• essential_gene_CRISPR: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.160

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sept12
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype

Gene ontology

• Biological process: spermatogenesis;cell differentiation;flagellated sperm motility;cytoskeleton-dependent cytokinesis
• Cellular component: stress fiber;nucleus;spindle;septin ring;microtubule cytoskeleton;midbody;septin complex;cleavage furrow;perinuclear region of cytoplasm;sperm annulus
• Molecular function: GTPase activity;protein binding;GTP binding;GDP binding;protein-containing complex scaffold activity;phosphatidylinositol binding;identical protein binding;protein homodimerization activity