Isolated growth hormone deficiency, type 5
disease diseaseOn this page
Also known as IGHD5pituitary hormone deficiency, combined or isolated, 7
Summary
Isolated growth hormone deficiency, type 5 (MONDO:0032569) is a disease caused by RNPC3 (GenCC Definitive), with 1 cohort gene.
At a glance
- Causal gene: RNPC3 (GenCC Definitive)
- Cohort genes: 1
- ClinVar variants: 19
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | isolated growth hormone deficiency, type 5 |
| Mondo ID | MONDO:0032569 |
| OMIM | 618160 |
| DOID | DOID:0061016 |
| UMLS | C4748435 |
| MedGen | 1648500 |
| GARD | 0025704 |
| Is cancer (heuristic) | no |
Also known as: IGHD5 · pituitary hormone deficiency, combined or isolated, 7
Data availability: 19 ClinVar variants · 4 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › combined pituitary hormone deficiencies, genetic form › isolated congenital growth hormone deficiency › isolated growth hormone deficiency, type 5
Related subtypes (6): isolated growth hormone deficiency type II, isolated growth hormone deficiency type IA, short stature due to growth hormone qualitative anomaly, isolated growth hormone deficiency type III, isolated growth hormone deficiency type IB, isolated growth hormone deficiency, type 4
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
19 retrieved; paginated sample, class counts are floors:
9 pathogenic, 7 uncertain significance, 2 benign, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1064669 | NM_017619.4(RNPC3):c.613C>T (p.Arg205Ter) | RNPC3 | Pathogenic | criteria provided, single submitter |
| 1064671 | NM_017619.4(RNPC3):c.1421del (p.Pro474fs) | RNPC3 | Pathogenic | no assertion criteria provided |
| 1064672 | NM_017619.4(RNPC3):c.1449A>T (p.Leu483Phe) | RNPC3 | Pathogenic | no assertion criteria provided |
| 1319998 | NM_017619.4(RNPC3):c.259C>T (p.Gln87Ter) | RNPC3 | Pathogenic | no assertion criteria provided |
| 1319999 | NM_017619.4(RNPC3):c.443G>C (p.Gly148Ala) | RNPC3 | Pathogenic | no assertion criteria provided |
| 1320000 | NM_017619.4(RNPC3):c.261dup (p.Leu88fs) | RNPC3 | Pathogenic | no assertion criteria provided |
| 1320001 | NM_017619.4(RNPC3):c.1228T>G (p.Phe410Val) | RNPC3 | Pathogenic | no assertion criteria provided |
| 587367 | NM_017619.4(RNPC3):c.1420C>A (p.Pro474Thr) | RNPC3 | Pathogenic | no assertion criteria provided |
| 587368 | NM_017619.4(RNPC3):c.1504C>T (p.Arg502Ter) | RNPC3 | Pathogenic | no assertion criteria provided |
| 3062137 | NM_017619.4(RNPC3):c.894-2A>G | RNPC3 | Likely pathogenic | criteria provided, single submitter |
| 2442236 | NM_017619.4(RNPC3):c.859G>A (p.Asp287Asn) | RNPC3 | Uncertain significance | criteria provided, single submitter |
| 3044994 | NM_017619.4(RNPC3):c.1025A>C (p.Asn342Thr) | RNPC3 | Uncertain significance | criteria provided, single submitter |
| 3045438 | NM_017619.4(RNPC3):c.1024A>C (p.Asn342His) | RNPC3 | Uncertain significance | criteria provided, single submitter |
| 3068053 | NM_017619.4(RNPC3):c.1421C>T (p.Pro474Leu) | RNPC3 | Uncertain significance | criteria provided, single submitter |
| 3377745 | NM_017619.4(RNPC3):c.48CTC[2] (p.Ser19del) | RNPC3 | Uncertain significance | criteria provided, single submitter |
| 3775761 | NM_017619.4(RNPC3):c.1328A>G (p.Tyr443Cys) | RNPC3 | Uncertain significance | criteria provided, single submitter |
| 3892308 | NM_017619.4(RNPC3):c.344C>T (p.Ser115Phe) | RNPC3 | Uncertain significance | criteria provided, single submitter |
| 1327962 | NM_017619.4(RNPC3):c.342C>T (p.Gly114=) | RNPC3 | Benign | criteria provided, multiple submitters, no conflicts |
| 1327963 | NM_017619.4(RNPC3):c.359+16A>G | RNPC3 | Benign | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| RNPC3 | Definitive | Autosomal recessive | isolated growth hormone deficiency, type 5 | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| RNPC3 | Orphanet:231662 | Isolated growth hormone deficiency type IA |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| RNPC3 | HGNC:18666 | ENSG00000185946 | Q96LT9 | RNA-binding region-containing protein 3 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| RNPC3 | RNA-binding region-containing protein 3 | Participates in pre-mRNA U12-dependent splicing, performed by the minor spliceosome which removes U12-type introns. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Other/Unknown | 1 | 1.8× | 0.558 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| RNPC3 | Other/Unknown | no | RRM_dom, Nucleotide-bd_a/b_plait_sf, RBM40_RRM1 |
Expression context
Cohort genes with no expression data: 0.
1 cohort gene are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 1 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| caput epididymis | 1 |
| corpus epididymis | 1 |
| right uterine tube | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| RNPC3 | 256 | ubiquitous | marker | caput epididymis, corpus epididymis, right uterine tube |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| RNPC3 | 1,863 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| RNPC3 | Q96LT9 | 2 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| mRNA Splicing - Minor Pathway | 1 | 223.9× | 0.016 | RNPC3 |
| mRNA Splicing | 1 | 109.8× | 0.016 | RNPC3 |
| Processing of Capped Intron-Containing Pre-mRNA | 1 | 82.2× | 0.016 | RNPC3 |
| Metabolism of RNA | 1 | 41.7× | 0.024 | RNPC3 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| mRNA splicing, via spliceosome | 1 | 91.6× | 0.011 | RNPC3 |
| RNA splicing | 1 | 88.2× | 0.011 | RNPC3 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| RNPC3 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | RNPC3 |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| RNPC3 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: RNPC3