SP140L

Chr 2

SP140 like nuclear body protein

NCBI Gene: 93349 ENSG00000185404 UniProt: Q9H930 OMIM: 617747

SP140L encodes a predicted nuclear transcription factor that binds DNA and regulates RNA polymerase II-mediated transcription. The gene is highly constrained against loss-of-function variants (pLI near 0), but no definitive human disease associations have been established for SP140L mutations. Further research is needed to determine if variants in this gene cause pediatric neurological disorders.

OMIM ResearchSummary from RefSeq

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm and nucleolus. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.80

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.80LOEUF

pLI 0.000

Z-score 2.51

OE 0.54 (0.38–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.09Z-score

OE missense 1.01 (0.92–1.12)

297 obs / 292.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.54 (0.38–0.80)

0≤0.351.4

Missense OE?1.01 (0.92–1.12)

0≤0.61.4

Synonymous OE?1.10

0≤1.21.6

LoF obs/exp: 19 / 35.1Missense obs/exp: 297 / 292.8Syn Z: -0.78

Background carrier burden — how many people carry a rare variant somewhere in SP140L?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 77

687 rare PASS variants

Rare truncating (LoF)

1 in 500

125 rare PASS variants

Rare synonymous (reference)

1 in 190

260 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SP140L. 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 110	1 in 530
South Asian	~43k	1 in 80	1 in 830
Remaining (unassigned)	~30k	1 in 62	1 in 660
European (Finnish)	~27k	1 in 400	1 in 3,800
Admixed American	~22k	1 in 60	1 in 460
African / African American	~21k	1 in 69	1 in 480
East Asian	~20k	1 in 77	1 in 1,000
Ashkenazi Jewish	~13k	1 in 800	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 120	1 in 350

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): 15 of 19 coding exons well covered in gnomAD exomes; exons 13, 16, 17, 18 marginal. Genomes: 16 of 19 (exons 16, 17, 18 below).? see exons ↓