MOSPD2

Chr X

motile sperm domain containing 2

NCBI Gene: 158747 ENSG00000130150 UniProt: Q8NHP6 OMIM: 301086

The MOSPD2 protein mediates formation of contact sites between the endoplasmic reticulum and other organelles including endosomes, mitochondria, and Golgi, and participates in lipid droplet homeostasis. Mutations cause autosomal recessive intellectual disability with developmental delay, and the gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.26). The condition primarily affects neurological development and cognitive function.

OMIM ResearchSummary from RefSeq, UniProt

Enables FFAT motif binding activity. Involved in lipid droplet formation; positive regulation of leukocyte chemotaxis; and protein homooligomerization. Located in endoplasmic reticulum membrane; endoplasmic reticulum-endosome membrane contact site; and plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.26

Clinical Summary— MOSPD2

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

28 VUS of 154 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.26LOEUF

pLI 0.991

Z-score 3.78

OE 0.05 (0.02–0.26)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.66Z-score

OE missense 0.65 (0.56–0.76)

115 obs / 177.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.26)

0≤0.351.4

Missense OE?0.65 (0.56–0.76)

0≤0.61.4

Synonymous OE?0.62

0≤1.21.6

LoF obs/exp: 1 / 18.5Missense obs/exp: 115 / 177.2Syn Z: 2.32

This gene — mechanism propensity

0.2698th %ile

GOF

0.4184th %ile

LOF

0.68top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.26

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

154 submitted variants in ClinVar

ClinVar

Classification Summary

VUS28

Likely Benign2

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	28	0	0	28
Likely Benign	1	0	1	2
Benign	0	1	1	2
Total	29	1	2	32

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

View in ClinVar →

70 pathogenic / likely-pathogenic (of 77) ClinVar copy-number / structural variants overlap MOSPD2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →