GeneBe

RLIM

protein-coding

ring finger protein, LIM domain interacting, the group of Ring finger proteins

Gene summary

The protein encoded by this gene is a RING-H2 zinc finger protein. It has been shown to be an E3 ubiquitin protein ligase that targets LIM domain binding 1 (LDB1/CLIM), and causes proteasome-dependent degradation of LDB1. This protein and LDB1 are co-repressors of LHX1/LIM-1, a homeodomain transcription factor. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Feb 2009]

Previous symbols:
  • RNF12

MANE transcript

NM_016120.4

Inheritance

XL, AD

ClinVar variants

P:14U:138B:36

Top phenotype

Tonne-Kalscheuer syndrome

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chrX:74,582,976-74,614,624

External References & Databases

Ensembl (ENSG00000131263)NCBI Gene (51132)OMIM (300379)HGNC:13429GenCCUniProt (Q9NVW2)AlphaFoldClinVar (RLIM)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~31.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

non-syndromic X-linked intellectual disabilityDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0019181

Submitter: Illumina

intellectual disability, X-linked 61MODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010506

Submitter: Ambry Genetics

intellectual disability, X-linked 61STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010506

Submitter: Labcorp Genetics (formerly Invitae)

intellectual disability, X-linked 61STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010506

Submitter: PanelApp Australia

syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0000508

Submitter: Orphanet

intellectual disability, X-linked 61STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010506

Submitter: Broad Center for Mendelian Genomics

intellectual disability, X-linked 61STRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010506

Submitter: G2P

Clinical Genomic Database (CGD)

Tonne-Kalscheuer syndromeXL

Manifestation: Craniofacial; Genitourinary; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 25644381; 25735484; 29728705Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RLIM variants in ClinVar

11 Conditions Cataloged
not providedTotal: 110
Inborn genetic diseasesTotal: 35
Intellectual disability, X-linked 61Total: 34
not specifiedTotal: 15
RLIM-related disorderTotal: 6
Non-syndromic X-linked intellectual disabilityTotal: 2
Prostate cancerTotal: 1
Joubert syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016120.4. 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.

EffectPLPVUSLBBSum
synonymous
6
clinvar
16
clinvar
2
clinvar
 24
missense
3
clinvar
11
clinvar
122
clinvar
17
clinvar
1
clinvar
 154
nonsense
4
clinvar
 4
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
4
clinvar
 4
Total311138333188

Highest pathogenic variant AF is 0.0000018418632

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_016120.4RefSeqNP_057204.23MANE Select
ENST00000332687.11EnsemblENSP00000328059.63MANE Select
NM_183353.3RefSeqNP_899196.13Standard
ENST00000349225.2EnsemblENSP00000253571.33Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
rlimDanio rerio

Structure: head

Quality: increased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Immune System
  • Adaptive Immune System
  • Antigen processing: Ubiquitination & Proteasome degradation
  • Class I MHC mediated antigen processing & presentation

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • protein polyubiquitination
  • ubiquitin-dependent protein catabolic process
  • protein ubiquitination
  • negative regulation of DNA-binding transcription factor activity

Molecular Function

  • transcription corepressor activity
  • ubiquitin-protein transferase activity
  • metal ion binding
  • ubiquitin protein ligase activity

Cellular Component

  • nucleus
  • nucleoplasm
  • cytosol
  • transcriptional repressor complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000332687
Coding exons
3
Length
29401
Individuals with no LoFs
125562
Homozygous LoFs
0
Heterozygous LoFs
1
Defined
125563
p
0.00000398
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.421362420.5620.00001914059
Missense (PolyPhen)525.2550.19798415
Synonymous-1.8410079.21.260.000005391261
Loss of Function3.85119.20.05200.00000194273

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000360.000029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: E3 ubiquitin-protein ligase. Acts as a negative coregulator for LIM homeodomain transcription factors by mediating the ubiquitination and subsequent degradation of LIM cofactors LDB1 and LDB2 and by mediating the recruitment the SIN3a/histone deacetylase corepressor complex. Ubiquitination and degradation of LIM cofactors LDB1 and LDB2 allows DNA-bound LIM homeodomain transcription factors to interact with other protein partners such as RLIM. Plays a role in telomere length-mediated growth suppression by mediating the ubiquitination and degradation of TERF1. By targeting ZFP42 for degradation, acts as an activator of random inactivation of X chromosome in the embryo, a stochastic process in which one X chromosome is inactivated to minimize sex- related dosage differences of X-encoded genes in somatic cells of female placental mammals. {ECO:0000269|PubMed:19164295, ECO:0000269|PubMed:19945382}.;

Recessive Scores

pRec
0.127

Intolerance Scores

LoFtool
0.0499
RVIS EVS
-0.25
RVIS percentile EVS
35.75

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
K
Indispensability pred.
E
Indispensability score
0.777

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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