RNPC3

RNA binding region (RNP1, RRM) containing 3, the group of RNA binding motif containing|U11/U12 di-snRNP

Basic information

Region (hg38): 1:103525691-103555239

Links

ENSG00000185946 ∙ NCBI:55599 ∙ OMIM:618016 ∙ HGNC:18666 ∙ Uniprot:Q96LT9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• isolated growth hormone deficiency type IA (Supportive), mode of inheritance: AR
• isolated growth hormone deficiency, type 5 (Definitive), mode of inheritance: AR
• isolated growth hormone deficiency, type 5 (Strong), mode of inheritance: AR
• isolated growth hormone deficiency, type 5 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pituitary hormone deficiency, combined or isolated, 7	AR	Endocrine	Individuals may have multiple hormonal deficiencies (eg, GH hormone deficiency, hypothyroidism), and awareness may allow prompt management to treat with relevant hormonal therapeutics	Craniofacial; Endocrine; Neurologic	24480542; 29866761; 32462814; 33650182

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNPC3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNPC3 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				5	1	6
missense			24	3	1	28
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region				1	1	2
non coding				1	1	2
Total	0	1	25	9	3

Variants in RNPC3

This is a list of pathogenic ClinVar variants found in the RNPC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-103526094-T-G			Likely benign (Mar 02, 2018)
1-103526216-A-G		Inborn genetic diseases	Uncertain significance (Jun 17, 2024)
1-103526246-CA-C			Uncertain significance (Jul 05, 2017)
1-103526250-T-A		RNPC3-related disorder	Benign (Sep 15, 2020)
1-103526256-G-T			Likely benign (May 25, 2018)
1-103533757-C-T		Isolated growth hormone deficiency, type 5	Pathogenic (Nov 05, 2021)
1-103533757-C-CA		Isolated growth hormone deficiency, type 5	Pathogenic (Nov 05, 2021)
1-103533826-T-C		Inborn genetic diseases	Uncertain significance (Apr 05, 2023)
1-103533840-C-T		Isolated growth hormone deficiency, type 5	Benign (Nov 07, 2021)
1-103533856-A-G		Inborn genetic diseases	Uncertain significance (Jun 28, 2022)
1-103533873-A-G		Isolated growth hormone deficiency, type 5	Benign (Nov 07, 2021)
1-103534778-G-A		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
1-103534857-G-C		Isolated growth hormone deficiency, type 5	Pathogenic (Nov 05, 2021)
1-103535434-A-G		Inborn genetic diseases	Uncertain significance (Sep 25, 2023)
1-103536119-C-T		RNPC3-related disorder	Likely benign (Apr 25, 2019)
1-103536183-C-A			Likely benign (Dec 01, 2022)
1-103536183-C-T		Decreased response to growth hormone stimulation test • Isolated growth hormone deficiency, type 5	Pathogenic (Nov 05, 2021)
1-103536184-G-A		Inborn genetic diseases	Uncertain significance (Nov 28, 2023)
1-103536187-C-T		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
1-103536195-G-T		Decreased response to growth hormone stimulation test	Pathogenic (Apr 05, 2021)
1-103537342-T-C		Inborn genetic diseases	Uncertain significance (Dec 06, 2022)
1-103537358-C-T		Inborn genetic diseases	Uncertain significance (May 15, 2023)
1-103537370-C-T		Inborn genetic diseases	Uncertain significance (Jul 20, 2021)
1-103537408-C-T		Inborn genetic diseases	Uncertain significance (Aug 10, 2023)
1-103537420-G-A		Inborn genetic diseases	Uncertain significance (Jun 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNPC3	protein_coding	protein_coding	ENST00000533099	14	29549

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000196	0.995	124530	0	10	124540	0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.990	178	219	0.812	0.0000107	3359
Missense in Polyphen		46	65.113	0.70646		929
Synonymous	0.227	74	76.5	0.967	0.00000373	960
Loss of Function	2.49	10	22.8	0.438	0.00000115	390

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000652	0.0000646
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000800	0.0000797
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Participates in pre-mRNA U12-dependent splicing, performed by the minor spliceosome which removes U12-type introns. U12-type introns comprises less than 1% of all non-coding sequences. Binds to the 3'-stem-loop of m(7)G-capped U12 snRNA. {ECO:0000269|PubMed:16096647, ECO:0000269|PubMed:19447915}.
• Pathway: Metabolism of RNA;mRNA Splicing - Minor Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Intolerance Scores

• loftool: 0.697
• rvis_EVS: -0.01
• rvis_percentile_EVS: 52.85

Haploinsufficiency Scores

• pHI: 0.0904
• hipred: N
• hipred_score: 0.231
• ghis: 0.629

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.802

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rnpc3

Zebrafish Information Network

• Gene name: rnpc3
• Affected structure: intestinal epithelium
• Phenotype tag: abnormal
• Phenotype quality: surface feature shape

Gene ontology

• Biological process: mRNA splicing, via spliceosome;RNA splicing
• Cellular component: nucleus;nucleoplasm;U12-type spliceosomal complex
• Molecular function: U12 snRNA binding;pre-mRNA intronic binding