SEMA5A

Chr 5

semaphorin 5A

Also known as: SEMAF, semF

NCBI Gene: 9037ENSG00000112902UniProt: Q13591

This gene belongs to the semaphorin gene family that encodes membrane proteins containing a semaphorin domain and several thrombospondin type-1 repeats. Members of this family are involved in axonal guidance during neural development. This gene has been implicated as an autism susceptibility gene.[provided by RefSeq, Jan 2010]

351
ClinVar variants
100
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SEMA5A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
100 Pathogenic / Likely Pathogenic· 174 VUS of 351 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.48LOEUF
pLI 0.000
Z-score 4.79
OE 0.33 (0.23–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.33Z-score
OE missense 0.86 (0.80–0.92)
573 obs / 670.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.23–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.80–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 20 / 60.1Missense obs/exp: 573 / 670.1Syn Z: -1.33

ClinVar Variant Classifications

351 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic100
VUS174
Likely Benign48
Benign26
Conflicting3
100
Pathogenic
174
VUS
48
Likely Benign
26
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
100
0
100
Likely Pathogenic
0
0
0
0
0
VUS
1
155
17
1
174
Likely Benign
0
6
11
31
48
Benign
0
3
1
22
26
Conflicting
—3
Total116412954351

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

View in ClinVar →

Protein Context — Lollipop Plot

SEMA5A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SEMAPHORIN 5A; SEMA5A
MIM #609297 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical significance of serum Sema5A and IGFBP-3 in type 2 diabetes mellitus with hyperthyroidism.
Deng Y et al.·Medicine (Baltimore)
2025
Identification of O-glycosylation related genes and subtypes in ulcerative colitis based on machine learning.
Lu Y et al.·PLoS One
2024
Semaphorin-5A maintains epithelial phenotype of malignant pancreatic cancer cells.
Saxena S et al.·BMC Cancer
2018
Exosome-derived miR-182-5p promoted cholangiocarcinoma progression and vasculogenesis by regulating ADK/SEMA5a/PI3K pathway.
Wang J et al.·Liver Int
2024
Identification and validation of immune-related biomarkers and potential regulators and therapeutic targets for diabetic kidney disease.
Chen S et al.·BMC Med Genomics
2023
FUS-mediated dysregulation of Sema5a, an autism-related gene, in FUS mice with hippocampus-dependent cognitive deficits.
Ho WY et al.·Hum Mol Genet
2019
Metabolic Dysfunction-Associated Steatotic Liver Disease Shapes a Distinct Semaphorin-Cytokine Immune Signature in Severe Community-Acquired Pneumonia.
Gjurašin B et al.·Int J Mol Sci
2025
Helicobacter pylori virulence factor CagA promotes Snail-mediated epithelial-mesenchymal transition and invasive behavior by downregulating Semaphorin 5A in gastric epithelial cells.
Kubo S et al.·Biochem Biophys Res Commun
2025
De novo mutations in idiopathic male infertility-A pilot study.
Hodžić A et al.·Andrology
2021
Identification of a novel biomarker, SEMA5A, for non-small cell lung carcinoma in nonsmoking women.
Lu TP et al.·Cancer Epidemiol Biomarkers Prev
2010
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools