MOSPD2

Chr X

motile sperm domain containing 2

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

Endoplasmic reticulum-anchored protein that mediates the formation of contact sites between the endoplasmic (ER) and endosomes, mitochondria or Golgi through interaction with conventional- and phosphorylated-FFAT-containing organelle-bound proteins (PubMed:29858488, PubMed:33124732, PubMed:35389430). In addition, forms endoplasmic reticulum (ER)-lipid droplets (LDs) contacts through a direct protein-membrane interaction and participates in LDs homeostasis (PubMed:35389430). The attachment mechanism involves an amphipathic helix that has an affinity for lipid packing defects present at the surface of LDs (PubMed:35389430). Promotes migration of primary monocytes and neutrophils, in response to various chemokines (PubMed:28137892)

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.26

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

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

Background carrier burden — how many people carry a rare variant somewhere in MOSPD2?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

336 rare PASS variants

Rare truncating (LoF)

1 in 25,000

13 rare PASS variants

Rare synonymous (reference)

1 in 490

131 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for MOSPD2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~561k	1 in 260	1 in 35,000
South Asian	~36k	1 in 180	none seen
Remaining (unassigned)	~31k	1 in 190	none seen
European (Finnish)	~27k	1 in 850	none seen
Admixed American	~23k	1 in 170	1 in 3,300
African / African American	~21k	1 in 180	≈ 1 in 17,000
East Asian	~20k	1 in 170	≈ 1 in 4,900
Ashkenazi Jewish	~13k	1 in 1,600	≈ 1 in 3,800
Middle Eastern	~2,757	1 in 190	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 11 of 15 coding exons well covered in gnomAD exomes; exons 4, 6, 7, 11 marginal. Genomes: all 15.? see exons ↓