SPTBN5

protein-coding

spectrin beta, non-erythrocytic 5, the group of MicroRNA protein coding host genes|Spectrins

Gene summary

Enables cytoskeletal protein binding activity; dynein intermediate chain binding activity; and identical protein binding activity. Acts upstream of or within Golgi organization and lysosomal transport. Located in cytoplasm; photoreceptor connecting cilium; and photoreceptor disc membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_016642.4

Inheritance

AD, AR

ClinVar variants

U:757B:187

Top phenotype

SPTBN5-related disorder

gnomAD constraint

pLI —, LoF o/e 0.94

Max pathogenic AF

—

Genomic locus

chr15:41,848,146-41,894,053

External References & Databases

Ensembl (ENSG00000137877)

Transcript & Mutation Effects

hg38 • Region Span ~45.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

multiple congenital anomalies/dysmorphic syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019042

Submitter: LiferaOmics

Genetic evidence – Published PMID: 32732226 – Family 1 – one proband. Case-level (AR compound heterozygous; one predicted null + one non-LOF missense; each variant evaluated independently; no consanguinity deduction applied) = 1.6; Segregation = 0; Case-control = 0 Family 1 total = 1.6 Published genetic evidence total = 1.6 / 12 Genetic evidence – Our cases Family 1 – One proband. Case-level (biallelic predicted null in AR model; homozygous frameshift; consanguinity −0.5 applied) = (1.5 − 0.5) = 1.0; Segregation = 0; Case-control = 0 Family 1 total = 1.0 Total genetic evidence (published AR + our case) 1.6 (published AR) + 1.0 (our case) = 2.6 / 12 Experimental evidence – Published PMID: 10764729 – Identification and characterization of βV-spectrin (SPTBN5), a cytoskeletal membrane-associated protein involved in cellular structural stability and organization. Gene function / biological plausibility = 0.5 (No patient-derived functional studies or animal NIHF model reported.) Experimental evidence total = 0.5 / 6 Overall score Genetic evidence = 2.6 Experimental evidence = 0.5 Overall score = 3.1 / 18

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPTBN5 variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 842

not providedTotal: 60

SPTBN5-related disorderTotal: 51

AutismTotal: 2

Moderate intellectual disabilityTotal: 2

Premature birthTotal: 2

See casesTotal: 2

Delayed speech and language developmentTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016642.4. 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			10 clinvar	37 clinvar	10 clinvar	57
missense			727 clinvar	131 clinvar	7 clinvar	865
nonsense			5 clinvar		1 clinvar	6
start loss						0
frameshift			6 clinvar			6
splice donor/acceptor (+/-2bp)			9 clinvar		1 clinvar	10
Total	0	0	757	168	19	944

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016642.4	RefSeq	NP_057726.4	67	MANE Select
ENST00000320955.8	Ensembl	ENSP00000317790.6	67	MANE Select
XM_017022299.2	RefSeq	XP_016877788.1	66	Standard
XM_017022302.2	RefSeq	XP_016877791.1	54	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Developmental Biology
Signal Transduction
Vesicle-mediated transport
Membrane Trafficking
Post-translational protein modification

Biological Process

MAPK cascade
endoplasmic reticulum to Golgi vesicle-mediated transport
Golgi organization
lysosomal transport
axon guidance

Molecular Function

actin binding
Ras guanyl-nucleotide exchange factor activity
kinesin binding
spectrin binding
myosin tail binding

Cellular Component

cytoplasm
microtubule organizing center
cytosol
spectrin
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000320955
Coding exons: 67
Length: 45931
Individuals with no LoFs: 121706
Homozygous LoFs: 35
Heterozygous LoFs: 2959
Defined: 124700
p: 0.0121

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.24	2146	1.99e+3	1.08	0.000129	23174
Missense (PolyPhen)		519	510.94	1.0158		7261
Synonymous	-1.01	903	865	1.04	0.0000532	7416
Loss of Function	0.772	186	198	0.941	0.0000104	2021

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0073	0.0068	notable
Latino/Admixed American	0.0060	0.0057	notable
Ashkenazi Jewish	0.0061	0.0061	notable
East Asian	0.036	0.036	notable
Finnish	0.012	0.011	notable
European (Non-Finnish)	0.0045	0.0044	notable
South Asian	0.040	0.040	notable
Other	0.012	0.011	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.121

Essentials

Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.143

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High