SP140

protein-coding

SP140 nuclear body protein, the group of PHD finger proteins|Bromodomain containing

Gene summary

This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 2016]

MANE transcript

NM_007237.5

Inheritance

—

ClinVar variants

U:120B:18

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr2:230,203,110-230,313,215

External References & Databases

Ensembl (ENSG00000079263)

Transcript & Mutation Effects

hg38 • Region Span ~110.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SP140 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 117

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007237.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	1 clinvar	2 clinvar	7
missense			110 clinvar	13 clinvar	2 clinvar	125
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	120	14	4	138

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 78 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007237.5	RefSeq	NP_009168.4	27	MANE Select
ENST00000392045.8	Ensembl	ENSP00000375899.3	27	MANE Select
NM_001005176.3	RefSeq	NP_001005176.1	4	Standard
NM_001278451.2	RefSeq	NP_001265380.1	26	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription, DNA-templated
defense response

Molecular Function

DNA binding
DNA-binding transcription factor activity
protein binding
metal ion binding

Cellular Component

fibrillar center
nucleus
nuclear envelope
nucleoplasm
mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392045
Coding exons: 27
Length: 155937
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 32
Defined: 125748
p: 0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.787	407	454	0.896	0.0000228	5738
Missense (PolyPhen)		93	134.63	0.69077		1838
Synonymous	1.12	146	164	0.889	0.00000920	1494
Loss of Function	4.00	22	53.6	0.410	0.00000254	688

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00039	0.00037	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the nuclear body, also known as nuclear domain 10, PML oncogenic domain, and KR body (PubMed:8910577). May be involved in the pathogenesis of acute promyelocytic leukemia and viral infection (PubMed:8910577). May play a role in chromatin-mediated regulation of gene expression although it does not bind to histone H3 tails (PubMed:24267382). {ECO:0000269|PubMed:24267382, ECO:0000269|PubMed:8910577, ECO:0000303|PubMed:8910577}.;

Recessive Scores

pRec: 0.0622

Intolerance Scores

LoFtool: 0.699
RVIS EVS: 0.32
RVIS percentile EVS: 72.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.730

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium