RBM28

protein-coding

RNA binding motif protein 28, the group of RNA binding motif containing

Gene summary

The protein encoded by this gene is a specific nucleolar component of the spliceosomal small nuclear ribonucleoprotein (snRNP)complexes . It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), possibly coordinating their transition through the nucleolus. Mutation in this gene causes alopecia, progressive neurological defects, and endocrinopathy (ANE syndrome), a pleiotropic and clinically heterogeneous disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

MANE transcript

NM_018077.3

Inheritance

ClinVar variants

P:4U:115B:36

Top phenotype

Alopecia, neurologic defects, and endocrinopathy syndrome

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr7:128,297,685-128,343,908

External References & Databases

Ensembl (ENSG00000106344)

Transcript & Mutation Effects

hg38 • Region Span ~46.2 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ANE syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0012794

Submitter: G2P

ANE syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0012794

Submitter: Orphanet

ANE syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012794

Submitter: Labcorp Genetics (formerly Invitae)

ANE syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0012794

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Alopecia, neurologic defects, and endocrinopathy syndromeAR

Manifestation: Dermatologic; Endocrine; Musculoskeletal; Neurologic

Intervention: Endocrine

Rationale: Features may include progressive endocrine abnormalities primarily related to progressive anterior pituitary hormone deficiency, including central adrenal insufficiency, as well as other endocrine deficiencies, and surveillance in order to allow appropriate hormonal replacement therapy may be beneficial

Refs: 18439547; 20231366

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RBM28 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 110

not providedTotal: 34

RBM28-related disorderTotal: 9

ANE syndromeTotal: 9

MicrocephalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018077.3. 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	20 clinvar	2 clinvar	24
missense	1 clinvar	1 clinvar	102 clinvar	12 clinvar	2 clinvar	118
nonsense			2 clinvar			2
start loss						0
frameshift		1 clinvar	4 clinvar			5
splice donor/acceptor (+/-2bp)	1 clinvar		5 clinvar			6
Total	2	2	115	32	4	155

Highest pathogenic variant AF is 0.0000074350733

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018077.3	RefSeq	NP_060547.2	19	MANE Select
ENST00000223073.6	Ensembl	ENSP00000223073.1	19	MANE Select
NM_001166135.2	RefSeq	NP_001159607.1	15	Standard
ENST00000415472.6	Ensembl	ENSP00000390517.2	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ribosome biogenesis in eukaryotes - Homo sapiens (human)

Biological Process

mRNA processing
RNA splicing

Molecular Function

RNA binding

Cellular Component

nucleus
spliceosomal complex
nucleolus
ribonucleoprotein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000223073
Coding exons: 19
Length: 46225
Individuals with no LoFs: 125644
Homozygous LoFs: 0
Heterozygous LoFs: 104
Defined: 125748
p: 0.000414

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.179	388	398	0.975	0.0000223	5010
Missense (PolyPhen)		175	178.82	0.97865		2181
Synonymous	0.768	139	151	0.921	0.00000872	1386
Loss of Function	2.52	25	42.8	0.584	0.00000236	532

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00045	0.00045	rare
South Asian	0.00078	0.00078	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Nucleolar component of the spliceosomal ribonucleoprotein complexes. {ECO:0000269|PubMed:17081119}.;

Recessive Scores

pRec: 0.0962

Intolerance Scores

LoFtool: 0.965
RVIS EVS: 1
RVIS percentile EVS: 90.77

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.936

Gene Damage Prediction

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