SAFB

protein-coding

scaffold attachment factor B, the group of RNA binding motif containing

Gene summary

This gene encodes a DNA-binding protein which has high specificity for scaffold or matrix attachment region DNA elements (S/MAR DNA). This protein is thought to be involved in attaching the base of chromatin loops to the nuclear matrix but there is conflicting evidence as to whether this protein is a component of chromatin or a nuclear matrix protein. Scaffold attachment factors are a specific subset of nuclear matrix proteins (NMP) that specifically bind to S/MAR. The encoded protein is thought to serve as a molecular base to assemble a 'transcriptosome complex' in the vicinity of actively transcribed genes. It is involved in the regulation of heat shock protein 27 transcription, can act as an estrogen receptor co-repressor and is a candidate for breast tumorigenesis. This gene is arranged head-to-head with a similar gene whose product has the same functions. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

MANE transcript

NM_001201338.2

Inheritance

—

ClinVar variants

U:108B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr19:5,623,035-5,668,478

External References & Databases

Ensembl (ENSG00000160633)

Transcript & Mutation Effects

hg38 • Region Span ~45.4 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 SAFB variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 100

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001201338.2. 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				2 clinvar	1 clinvar	3
missense			100 clinvar	3 clinvar		103
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	108	5	1	114

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 93 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001201338.2	RefSeq	NP_001188267.1	21	MANE Select
ENST00000588852.2	Ensembl	ENSP00000467423.1	21	MANE Select
NM_001201339.2	RefSeq	NP_001188268.1	21	Standard
NM_001201340.2	RefSeq	NP_001188269.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Structural Pathway of Interleukin 1 (IL-1)
Validated nuclear estrogen receptor alpha network

Biological Process

chromatin organization
regulation of transcription by RNA polymerase II
intracellular estrogen receptor signaling pathway
regulation of growth
hormone metabolic process

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
chromatin binding
double-stranded DNA binding
RNA binding
protein binding

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000588852
Coding exons: 21
Length: 45444
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125716
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.14	383	521	0.736	0.0000359	6002
Missense (PolyPhen)		78	137.23	0.5684		1753
Synonymous	-2.11	234	196	1.19	0.0000134	1717
Loss of Function	5.98	2	45.6	0.0439	0.00000254	578

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to scaffold/matrix attachment region (S/MAR) DNA and forms a molecular assembly point to allow the formation of a 'transcriptosomal' complex (consisting of SR proteins and RNA polymerase II) coupling transcription and RNA processing (By similarity). Can function as an estrogen receptor corepressor and can also bind to the HSP27 promoter and decrease its transcription. When associated with RBMX, binds to and stimulates transcription from the SREBF1 promoter (By similarity). Can inhibit cell proliferation. {ECO:0000250}.;

Recessive Scores

pRec: 0.157

Intolerance Scores

LoFtool: 0.0204
RVIS EVS: -1.62
RVIS percentile EVS: 2.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.920

Gene Damage Prediction

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