RLIM

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

Basic information

Region (hg38): X:74582976-74614624

Previous symbols: [ "RNF12" ]

Links

ENSG00000131263 ∙ NCBI:51132 ∙ OMIM:300379 ∙ HGNC:13429 ∙ Uniprot:Q9NVW2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: XLR
• intellectual disability, X-linked 61 (Strong), mode of inheritance: XL
• syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual disability, X-linked 61 (Moderate), mode of inheritance: XL
• non-syndromic X-linked intellectual disability (Definitive), mode of inheritance: XL
• intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tonne-Kalscheuer syndrome	XL	General	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	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	25644381; 25735484; 29728705

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RLIM gene.

• Intellectual disability, X-linked 61 (2 variants)
• Global developmental delay (1 variants)
• not provided (1 variants)
• Non-syndromic X-linked intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RLIM gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				7	3	10
missense	2	7	57	5	2	73
nonsense						0
start loss						0
frameshift						0
inframe indel			4	2		6
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1		1
Total	2	7	61	15	5

Variants in RLIM

This is a list of pathogenic ClinVar variants found in the RLIM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-74591450-C-T			Uncertain significance (Apr 13, 2024)
X-74591451-T-C		Inborn genetic diseases	Uncertain significance (Apr 29, 2021)
X-74591484-G-A		Intellectual disability, X-linked 61	Likely pathogenic (Aug 31, 2022)
X-74591520-G-A		Intellectual disability, X-linked 61	Pathogenic (Oct 11, 2018)
X-74591523-C-T		Intellectual disability, X-linked 61	Pathogenic/Likely pathogenic (Aug 16, 2022)
X-74591555-G-C		Intellectual disability, X-linked 61	Pathogenic (Oct 11, 2018)
X-74591572-G-C			Uncertain significance (Jun 08, 2022)
X-74591572-G-T			Uncertain significance (Feb 28, 2024)
X-74591586-A-G		Intellectual disability, X-linked 61	Likely pathogenic (Dec 05, 2018)
X-74591624-T-C		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
X-74591701-ATTT-C			Uncertain significance (Dec 21, 2021)
X-74591744-C-A			Uncertain significance (May 23, 2023)
X-74591744-C-T			Uncertain significance (May 09, 2017)
X-74591786-C-T		Intellectual disability, X-linked 61	Uncertain significance (Sep 22, 2024)
X-74591795-C-T		Inborn genetic diseases	Uncertain significance (Jun 04, 2021)
X-74591800-T-G			Likely benign (Mar 30, 2018)
X-74591807-G-A		Intellectual disability, X-linked 61	Uncertain significance (Jul 16, 2023)
X-74591825-T-C		Intellectual disability, X-linked 61	Uncertain significance (Jan 03, 2022)
X-74591847-A-T			Uncertain significance (Mar 30, 2022)
X-74591860-A-G			Likely benign (Aug 01, 2023)
X-74591861-C-A			Uncertain significance (Oct 28, 2022)
X-74591874-AACTGGAACTAGG-A			Likely benign (Dec 01, 2023)
X-74591879-G-C		Inborn genetic diseases	Uncertain significance (Feb 12, 2024)
X-74591884-A-C			Likely benign (Oct 01, 2022)
X-74591885-G-A			Uncertain significance (Aug 27, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RLIM	protein_coding	protein_coding	ENST00000332687	3	29401

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.993	0.00699	125562	0	1	125563	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.42	136	242	0.562	0.0000191	4059
Missense in Polyphen		5	25.255	0.19798		415
Synonymous	-1.84	100	79.2	1.26	0.00000539	1261
Loss of Function	3.85	1	19.2	0.0520	0.00000194	273

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000365	0.0000365
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

• pRec: 0.127

Intolerance Scores

• loftool: 0.0499
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.75

Haploinsufficiency Scores

• pHI: 0.779
• hipred: Y
• hipred_score: 0.785
• ghis: 0.548

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.777

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rlim
• Phenotype: cellular phenotype; reproductive system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype

Zebrafish Information Network

• Gene name: rlim
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: increased size

Gene ontology

• 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;negative regulation of transcription, DNA-templated;random inactivation of X chromosome;regulation of dosage compensation by inactivation of X chromosome
• Cellular component: nucleus;nucleoplasm;cytosol;transcriptional repressor complex
• Molecular function: transcription corepressor activity;ubiquitin-protein transferase activity;metal ion binding;ubiquitin protein ligase activity