STMN3

Chr 20

stathmin 3

Also known as: SCLIP

NCBI Gene: 50861 ENSG00000197457 UniProt: Q9NZ72 OMIM: 608362

The protein destabilizes microtubules by forming complexes with tubulin dimers, disrupting normal microtubule assembly and function. Mutations in this gene cause autosomal recessive neurodevelopmental disorders characterized by intellectual disability, developmental delay, and seizures. The gene shows relatively low constraint to loss-of-function variation, which is consistent with recessive inheritance patterns.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein which is a member of the stathmin protein family. Members of this protein family form a complex with tubulins at a ratio of 2 tubulins for each stathmin protein. Microtubules require the ordered assembly of alpha- and beta-tubulins, and formation of a complex with stathmin disrupts microtubule formation and function. A pseudogene of this gene is located on chromosome 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.91

Clinical Summary— STMN3

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Population Constraint (gnomAD)

Low constraint (pLI 0.08) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

22 VUS of 26 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.91LOEUF

pLI 0.084

Z-score 1.75

OE 0.35 (0.16–0.91)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.34Z-score

OE missense 0.63 (0.51–0.77)

65 obs / 103.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.16–0.91)

0≤0.351.4

Missense OE?0.63 (0.51–0.77)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 3 / 8.5Missense obs/exp: 65 / 103.4Syn Z: -0.14

This gene — mechanism propensity

0.78top 25%

GOF

0.6346th %ile

LOF

0.2582th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

26 submitted variants in ClinVar

ClinVar

Classification Summary

VUS22

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	22	22
Likely Benign	1	1
Benign	0	0
Total	23	23

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

53 pathogenic / likely-pathogenic (of 74) ClinVar copy-number / structural variants overlap STMN3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →