SEPTIN12

protein-coding

septin 12, the group of Septins

Gene summary

This gene encodes a guanine-nucleotide binding protein and member of the septin family of cytoskeletal GTPases. Septins play important roles in cytokinesis, exocytosis, embryonic development, and membrane dynamics. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

Previous symbols:

SEPT12

MANE transcript

NM_144605.5

Inheritance

AD, AR

ClinVar variants

U:92B:11

Top phenotype

Spermatogenic failure 10

gnomAD constraint

pLI —, LoF o/e 1.43

Max pathogenic AF

—

Genomic locus

chr16:4,777,606-4,788,398

External References & Databases

Ensembl (ENSG00000140623)

Transcript & Mutation Effects

hg38 • Region Span ~10.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 10LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013901

Submitter: Labcorp Genetics (formerly Invitae)

non-syndromic male infertility due to sperm motility disorderSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017173

Submitter: Orphanet

Clinical Genomic Database (CGD)

Spermatogenic failure 10AD

Manifestation: Genitourinary

Intervention: General

Rationale: 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

Refs: 22275165; 22479503

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEPTIN12 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 93

Spermatogenic failure 10Total: 6

not providedTotal: 4

SEPTIN12-related disorderTotal: 3

Non-syndromic male infertility due to sperm motility disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144605.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	6 clinvar		7
missense			89 clinvar	5 clinvar		94
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	92	11	0	103

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144605.5	RefSeq	NP_653206.2	9	MANE Select
ENST00000268231.13	Ensembl	ENSP00000268231.8	9	MANE Select
NM_001154458.3	RefSeq	NP_001147930.1	8	Standard
ENST00000396693.10	Ensembl	ENSP00000379922.4	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Bacterial invasion of epithelial cells - Homo sapiens (human)

Biological Process

spermatogenesis
cell differentiation
flagellated sperm motility
cytoskeleton-dependent cytokinesis

Molecular Function

GTPase activity
protein binding
GTP binding
GDP binding
protein-containing complex scaffold activity

Cellular Component

stress fiber
nucleus
spindle
septin ring
microtubule cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000268231
Coding exons: 9
Length: 10853
Individuals with no LoFs: 125559
Homozygous LoFs: 0
Heterozygous LoFs: 189
Defined: 125748
p: 0.000752

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.54	292	227	1.29	0.0000145	2339
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00076	0.00068	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.0073	0.0073	notable
East Asian	0.00060	0.00060	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00031	0.00031	rare
South Asian	0.0014	0.0014	notable
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.805
RVIS EVS: -0.38
RVIS percentile EVS: 28.01

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.160

Gene Damage Prediction

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