CST7

Chr 20

cystatin F

Also known as: CMAP

NCBI Gene: 8530 ENSG00000077984 UniProt: O76096 OMIM: 603253

CST7 encodes a glycosylated cysteine protease inhibitor that inhibits papain and cathepsin L and may regulate immune function through inhibition of targets in the hematopoietic system. Mutations cause autosomal recessive cerebellar ataxia with seizures and intellectual disability, with onset typically in early childhood. This gene is not highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions. This gene encodes a glycosylated cysteine protease inhibitor with a putative role in immune regulation through inhibition of a unique target in the hematopoietic system. Expression of the protein has been observed in various human cancer cell lines established from malignant tumors. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.92

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.92LOEUF

pLI 0.000

Z-score -1.03

OE 1.45 (0.83–1.92)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.60Z-score

OE missense 1.18 (1.01–1.40)

100 obs / 84.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.45 (0.83–1.92)

0≤0.351.4

Missense OE?1.18 (1.01–1.40)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 9 / 6.2Missense obs/exp: 100 / 84.4Syn Z: -0.09

Background carrier burden — how many people carry a rare variant somewhere in CST7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

205 rare PASS variants

Rare truncating (LoF)

1 in 950

59 rare PASS variants

Rare synonymous (reference)

1 in 410

78 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CST7. 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 280	1 in 1,400
South Asian	~43k	1 in 290	1 in 580
Remaining (unassigned)	~30k	1 in 400	1 in 1,400
European (Finnish)	~27k	1 in 1,000	≈ 1 in 27,000
Admixed American	~22k	1 in 180	1 in 530
African / African American	~21k	1 in 210	1 in 650
East Asian	~20k	1 in 160	1 in 860
Ashkenazi Jewish	~13k	≈ 1 in 6,500	1 in 2,200
Middle Eastern	~2,884	1 in 290	≈ 1 in 580

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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓