SEMA3D

Chr 7

semaphorin 3D

Also known as: Sema-Z2, coll-2

NCBI Gene: 223117ENSG00000153993UniProt: O95025

This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016]

289
ClinVar variants
12
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SEMA3D
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 178 VUS of 289 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.66LOEUF
pLI 0.000
Z-score 3.37
OE 0.45 (0.32–0.66)
Tolerant

Typical tolerance to LoF variation

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.
0.76Z-score
OE missense 0.90 (0.82–0.98)
371 obs / 414.2 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.0.45 (0.32–0.66)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.82–0.98)
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.1.03
0≤1.21.6
LoF obs/exp: 20 / 44.2Missense obs/exp: 371 / 414.2Syn Z: -0.30

ClinVar Variant Classifications

289 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic1
VUS178
Likely Benign82
Benign16
Conflicting1
11
Pathogenic
1
Likely Pathogenic
178
VUS
82
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
10
0
11
Likely Pathogenic
0
0
1
0
1
VUS
4
157
17
0
178
Likely Benign
0
7
21
54
82
Benign
0
2
6
8
16
Conflicting
—1
Total41675562289

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

View in ClinVar →

Protein Context — Lollipop Plot

SEMA3D · 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 3D; SEMA3D
MIM #609907 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic architecture of Meniere's disease.
Gallego-Martinez A et al.·Hear Res
2020Review
Towards personalized medicine in Ménière's disease.
Lopez-Escamez JA et al.·F1000Res
2018Review
Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere's disease.
Martín-Sierra C et al.·Eur J Hum Genet
2017
Semaphorin 3D inhibits proliferation and migration of papillary thyroid carcinoma by regulating MAPK/ERK signaling pathway.
Hai R et al.·Mol Biol Rep
2022
Citrullinated IGF2BP1 promotes rheumatoid synovial aggression via increasing the mRNA stability of SEMA3D.
Qin Y et al.·Commun Biol
2025
CTNNA3 and SEMA3D: Promising loci for asthma exacerbation identified through multiple genome-wide association studies.
McGeachie MJ et al.·J Allergy Clin Immunol
2015
Molecular Pathways and Animal Models of Atrial Septal Defect.
Magnan RA et al.·Adv Exp Med Biol
2024Review
Systematic Review of Sequencing Studies and Gene Expression Profiling in Familial Meniere Disease.
Escalera-Balsera A et al.·Genes (Basel)
2020Review
Decreased expression of semaphorin 3D is associated with genesis and development in colorectal cancer.
Wang Z et al.·World J Surg Oncol
2017
Rare gene variants and weight loss at 10 years after sleeve gastrectomy and gastric bypass - a randomized clinical trial.
Loid P et al.·Surg Obes Relat Dis
2025
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