SSRP1

Chr 11

structure specific recognition protein 1

Also known as: FACT, FACT80, T160

NCBI Gene: 6749 ENSG00000149136 UniProt: Q08945 OMIM: 604328

The protein encoded by this gene is a subunit of a heterodimer that, along with SUPT16H, forms chromatin transcriptional elongation factor FACT. FACT interacts specifically with histones H2A/H2B to effect nucleosome disassembly and transcription elongation. FACT and cisplatin-damaged DNA may be crucial to the anticancer mechanism of cisplatin. This encoded protein contains a high mobility group box which most likely constitutes the structure recognition element for cisplatin-modified DNA. This protein also functions as a co-activator of the transcriptional activator p63. An alternatively spliced transcript variant of this gene has been described, but its full-length nature is not known. [provided by RefSeq, Jul 2008]

OMIM Research

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

0.28

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.28LOEUF

pLI 0.996

Z-score 4.98

OE 0.13 (0.07–0.28)

Highly constrained

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

Missense Constraint?

4.04Z-score

OE missense 0.45 (0.40–0.50)

189 obs / 422.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.13 (0.07–0.28)

0≤0.351.4

Missense OE?0.45 (0.40–0.50)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 5 / 38.3Missense obs/exp: 189 / 422.7Syn Z: 1.25

Background carrier burden — how many people carry a rare variant somewhere in SSRP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

553 rare PASS variants

Rare truncating (LoF)

1 in 5,700

53 rare PASS variants

Rare synonymous (reference)

1 in 110

336 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SSRP1. 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 190	1 in 5,500
South Asian	~43k	1 in 160	1 in 8,400
Remaining (unassigned)	~30k	1 in 93	≈ 1 in 15,000
European (Finnish)	~27k	1 in 670	≈ 1 in 27,000
Admixed American	~22k	1 in 180	≈ 1 in 11,000
African / African American	~21k	1 in 120	≈ 1 in 6,900
East Asian	~20k	1 in 150	≈ 1 in 19,000
Ashkenazi Jewish	~13k	1 in 1,600	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 220	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): All 16 coding exons well covered in gnomAD exomes and genomes.? see exons ↓