SP100

Chr 2

SP100 nuclear antigen

ENSG00000067066 UniProt: P23497 OMIM: 604585

SP100 encodes a major component of PML nuclear bodies that functions as a transcriptional coactivator and corepressor, regulating cell growth, differentiation, apoptosis, and viral responses. Mutations cause autosomal dominant immunodeficiency with anti-interferon autoantibodies and susceptible infections, typically presenting in childhood. The gene is highly constrained against loss-of-function variants, indicating intolerance to protein disruption.

OMIM ResearchSummary from RefSeq, UniProt

Together with PML, this tumor suppressor is a major constituent of the PML bodies, a subnuclear organelle involved in a large number of physiological processes including cell growth, differentiation and apoptosis. Functions as a transcriptional coactivator of ETS1 and ETS2 according to PubMed:11909962. Under certain conditions, it may also act as a corepressor of ETS1 preventing its binding to DNA according to PubMed:15247905. Through the regulation of ETS1 it may play a role in angiogenesis, controlling endothelial cell motility and invasion. Through interaction with the MRN complex it may be involved in the regulation of telomeres lengthening. May also regulate TP53-mediated transcription and through CASP8AP2, regulate FAS-mediated apoptosis. Also plays a role in infection by viruses, including human cytomegalovirus and Epstein-Barr virus, through mechanisms that may involve chromatin and/or transcriptional regulation

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.68

LOEUF

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.000

Z-score 3.55

OE 0.50 (0.37–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.60Z-score

OE missense 0.92 (0.85–1.00)

426 obs / 462.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.50 (0.37–0.68)

0≤0.351.4

Missense OE?0.92 (0.85–1.00)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 29 / 58.3Missense obs/exp: 426 / 462.1Syn Z: 1.42

Background carrier burden — how many people carry a rare variant somewhere in SP100?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 70

1,287 rare PASS variants

Rare truncating (LoF)

1 in 400

225 rare PASS variants

Rare synonymous (reference)

1 in 86

440 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SP100. 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 97	1 in 440
South Asian	~43k	1 in 39	1 in 670
Remaining (unassigned)	~30k	1 in 56	1 in 300
European (Finnish)	~27k	1 in 210	1 in 3,300
Admixed American	~22k	1 in 59	1 in 590
African / African American	~21k	1 in 41	1 in 380
East Asian	~20k	1 in 58	1 in 760
Ashkenazi Jewish	~13k	1 in 290	≈ 1 in 11,000
Middle Eastern	~2,884	1 in 51	1 in 480

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): 17 of 29 coding exons well covered in gnomAD exomes; exon 17 poorly covered; exons 5, 8, 11, 12, 14 and 6 more marginal. Genomes: all 29.? see exons ↓