SEPTIN5

protein-coding

septin 5, the group of Septins

Gene summary

This gene is a member of the septin gene family of nucleotide binding proteins, originally described in yeast as cell division cycle regulatory proteins. Septins are highly conserved in yeast, Drosophila, and mouse and appear to regulate cytoskeletal organization. Disruption of septin function disturbs cytokinesis and results in large multinucleate or polyploid cells. This gene is mapped to 22q11, the region frequently deleted in DiGeorge and velocardiofacial syndromes. A translocation involving the MLL gene and this gene has also been reported in patients with acute myeloid leukemia. Alternative splicing results in multiple transcript variants. The presence of a non-consensus polyA signal (AACAAT) in this gene also results in read-through transcription into the downstream neighboring gene (GP1BB; platelet glycoprotein Ib), whereby larger, non-coding transcripts are produced. [provided by RefSeq, Dec 2010]

Previous symbols:

PNUTL1
SEPT5

MANE transcript

NM_002688.6

Inheritance

—

ClinVar variants

P:1U:41B:11

Top phenotype

Abnormal bleeding

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr22:19,714,503-19,724,224

External References & Databases

Ensembl (ENSG00000184702)

Transcript & Mutation Effects

hg38 • Region Span ~9.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEPTIN5 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 46

not providedTotal: 8

Abnormal bleedingTotal: 1

MacrothrombocytopeniaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002688.6. 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				9 clinvar	1 clinvar	10
missense			41 clinvar	1 clinvar		42
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	0	1	41	10	1	53

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002688.6	RefSeq	NP_002679.2	12	MANE Select
ENST00000455784.7	Ensembl	ENSP00000391311.2	12	MANE Select
NM_001009939.3	RefSeq	NP_001009939.1	10	Standard
ENST00000383045.7	Ensembl	ENSP00000372515.3	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Parkinson,s disease - Homo sapiens (human)
Parkin-Ubiquitin Proteasomal System pathway
Parkinsons Disease Pathway

Biological Process

synaptic vesicle targeting
regulation of exocytosis
cytoskeleton-dependent cytokinesis
regulation of synaptic vesicle exocytosis

Molecular Function

GTPase activity
structural molecule activity
protein binding
GTP binding
protein-containing complex scaffold activity

Cellular Component

plasma membrane
septin ring
synaptic vesicle
microtubule cytoskeleton
septin complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000455784
Coding exons: 12
Length: 10309
Individuals with no LoFs: 125521
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125528
p: 0.0000279

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.63	128	243	0.526	0.0000157	2459
Missense (PolyPhen)		58	120.16	0.48268		1137
Synonymous	-0.749	111	101	1.09	0.00000727	664
Loss of Function	3.70	3	21.6	0.139	0.00000106	245

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Filament-forming cytoskeletal GTPase (By similarity). May play a role in cytokinesis (Potential). May play a role in platelet secretion (By similarity). {ECO:0000250, ECO:0000305}.;

Recessive Scores

pRec: 0.278

Intolerance Scores

LoFtool: 0.413
RVIS EVS: -0.34
RVIS percentile EVS: 30.07

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.998

Gene Damage Prediction

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