SDF4

Chr 1

stromal cell derived factor 4

NCBI Gene: 51150 ENSG00000078808 UniProt: Q9BRK5 OMIM: 614282

The protein is a stromal cell-derived factor containing calcium-binding motifs that localizes to the Golgi lumen and may regulate calcium-dependent cellular activities in the endoplasmic reticulum and post-ER compartments. Mutations cause autosomal recessive spastic tetraplegia with thin corpus callosum and progressive microcephaly, affecting the central nervous system with early childhood onset. The gene shows relatively low constraint to loss-of-function variation.

OMIM ResearchSummary from RefSeq, UniProt

May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.76

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.76LOEUF

pLI 0.009

Z-score 2.24

OE 0.39 (0.21–0.76)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.55Z-score

OE missense 0.90 (0.81–1.01)

227 obs / 251.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.21–0.76)

0≤0.351.4

Missense OE?0.90 (0.81–1.01)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 6 / 15.5Missense obs/exp: 227 / 251.7Syn Z: -0.46

Background carrier burden — how many people carry a rare variant somewhere in SDF4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 80

584 rare PASS variants

Rare truncating (LoF)

1 in 1,500

71 rare PASS variants

Rare synonymous (reference)

1 in 110

284 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SDF4. 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)	~556k	1 in 120	1 in 1,400
South Asian	~43k	1 in 72	1 in 1,500
Remaining (unassigned)	~30k	1 in 78	1 in 1,300
European (Finnish)	~27k	1 in 320	1 in 3,800
Admixed American	~22k	1 in 70	1 in 3,700
African / African American	~21k	1 in 70	1 in 1,100
East Asian	~20k	1 in 82	1 in 2,200
Ashkenazi Jewish	~13k	1 in 540	≈ 1 in 12,000
Middle Eastern	~2,884	1 in 83	≈ 1 in 2,800

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): 6 of 6 coding exons well covered in gnomAD exomes. Genomes: 5 of 6 (exon 3 below).? see exons ↓