RNPC3

Summary

RNPC3 (RNA binding region (RNP1, RRM) containing 3, HGNC:18666) is a protein-coding gene on chromosome 1p21.1, encoding RNA-binding region-containing protein 3 (Q96LT9). Participates in pre-mRNA U12-dependent splicing, performed by the minor spliceosome which removes U12-type introns. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

Two types of spliceosomes catalyze splicing of pre-mRNAs. The major U2-type spliceosome is found in all eukaryotes and removes U2-type introns, which represent more than 99% of pre-mRNA introns. The minor U12-type spliceosome is found in some eukaryotes and removes U12-type introns, which are rare and have distinct splice consensus signals. The U12-type spliceosome consists of several small nuclear RNAs and associated proteins. This gene encodes a 65K protein that is a component of the U12-type spliceosome. This protein contains two RNA recognition motifs (RRMs), suggesting that it may contact one of the small nuclear RNAs of the minor spliceosome.

Source: NCBI Gene 55599 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isolated growth hormone deficiency, type 5 (Definitive, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 100 total — 10 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 11
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_017619

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18666
Approved symbol	RNPC3
Name	RNA binding region (RNP1, RRM) containing 3
Location	1p21.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1839, FLJ20008, RBM40, SNRNP65
Ensembl gene	ENSG00000185946
Ensembl biotype	protein_coding
OMIM	618016
Entrez	55599

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000423855, ENST00000524631, ENST00000524641, ENST00000525323, ENST00000527062, ENST00000531883, ENST00000532117, ENST00000533099, ENST00000533834, ENST00000878138, ENST00000878139, ENST00000878140, ENST00000878141, ENST00000878142, ENST00000878143, ENST00000878144, ENST00000878145, ENST00000934247, ENST00000947124, ENST00000947125, ENST00000947126, ENST00000947127

RefSeq mRNA: 1 — MANE Select: NM_017619 NM_017619

CCDS: CCDS781

Canonical transcript exons

ENST00000423855 — 15 exons

Exon	Start	End
ENSE00001451721	103525699	103526262
ENSE00001647580	103555034	103555239
ENSE00001740086	103536126	103536194
ENSE00001768133	103551721	103551792
ENSE00001773484	103546248	103546342
ENSE00001781335	103544941	103545102
ENSE00001788530	103543296	103543447
ENSE00001803656	103537342	103537484
ENSE00003513940	103527695	103527742
ENSE00003548173	103533739	103533857
ENSE00003595213	103534774	103534857
ENSE00003614734	103550941	103551073
ENSE00003786232	103535330	103535441
ENSE00003787118	103541350	103541475
ENSE00003789575	103546977	103547035

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 96.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.7805 / max 401.9012, expressed in 1802 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4295	15.6640	1755
4296	8.1639	1634
4294	0.5324	295
4297	0.3043	142
4298	0.1158	34

Top tissues by expression

256 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
caput epididymis	UBERON:0004358	96.61	gold quality
corpus epididymis	UBERON:0004359	96.26	gold quality
right uterine tube	UBERON:0001302	96.02	gold quality
kidney epithelium	UBERON:0004819	95.68	gold quality
calcaneal tendon	UBERON:0003701	95.21	gold quality
sural nerve	UBERON:0015488	95.14	gold quality
body of pancreas	UBERON:0001150	94.98	gold quality
left lobe of thyroid gland	UBERON:0001120	94.42	gold quality
cauda epididymis	UBERON:0004360	94.30	gold quality
right lobe of thyroid gland	UBERON:0001119	94.22	gold quality
thyroid gland	UBERON:0002046	94.21	gold quality
renal medulla	UBERON:0000362	94.09	gold quality
mucosa of stomach	UBERON:0001199	94.09	gold quality
cortex of kidney	UBERON:0001225	93.89	gold quality
tibial nerve	UBERON:0001323	93.73	gold quality
corpus callosum	UBERON:0002336	93.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.06	gold quality
left ovary	UBERON:0002119	93.00	gold quality
right ovary	UBERON:0002118	92.95	gold quality
lateral globus pallidus	UBERON:0002476	92.94	gold quality
tendon	UBERON:0000043	92.82	gold quality
nipple	UBERON:0002030	92.79	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.63	gold quality
buccal mucosa cell	CL:0002336	92.36	gold quality
cerebellar hemisphere	UBERON:0002245	92.34	gold quality
cerebellar cortex	UBERON:0002129	92.33	gold quality
postcentral gyrus	UBERON:0002581	92.30	gold quality
right lung	UBERON:0002167	92.27	gold quality
endocervix	UBERON:0000458	92.25	gold quality
body of uterus	UBERON:0009853	92.16	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	4841.27
E-GEOD-131882	yes	2883.97
E-ANND-3	yes	9.26
E-CURD-135	no	3431.85
E-GEOD-99795	no	34.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting RNPC3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-6768-3P	99.14	67.38	1319
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-6780A-3P	98.42	67.49	1518

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• U11/U12-65K contribute to di-snRNP formation and intron bridging in the minor prespliceosome (PMID:16096647)
• Exome analysis of one proband revealed missense (c.1320C>A, p.P474T) and nonsense (c.1504C>T, p.R502X) mutations in the RNPC3 gene. (PMID:24480542)
• Study shows that the C-terminal RNA recognition motif of p65 binds to the distal 3’ stem-loop of U6atac. By using a binary splice site mutation suppressor assay, results demonstrate that p65 protein-binding apical stem-loop of U12 snRNA can be replaced by this U6atac distal 3’ stem-loop. (PMID:27510544)
• The authores propose that both the C-RRM folding defect and nonsense-mediated decay (NMD)-mediated decrease in the levels of the U11/U12-65K protein reduce formation of the U12-type intron recognition complex and missplicing of a subset of minor introns leading to pituitary hypoplasia and a subsequent defect in growth hormone secretion. (PMID:29255062)
• Expanding the phenotype of biallelic RNPC3 variants associated with growth hormone deficiency. (PMID:32462814)
• Establishing intellectual disability as the key feature of patients with biallelic RNPC3 variants. (PMID:33650182)
• Pathogenic variants in RNPC3 are associated with hypopituitarism and primary ovarian insufficiency. (PMID:34906446)
• A Novel RNPC3 Gene Variant Expands the Phenotype in Patients with Congenital Hypopituitarism and Neuropathy. (PMID:37463572)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnpc3	ENSDARG00000011247
mus_musculus	Rnpc3	ENSMUSG00000027981
rattus_norvegicus	Rnpc3	ENSRNOG00000017310
drosophila_melanogaster	CG44249	FBGN0265184

Paralogs (1): RBM41 (ENSG00000089682)

Protein

Protein identifiers

RNA-binding region-containing protein 3 — Q96LT9 (reviewed: Q96LT9)

Alternative names: RNA-binding motif protein 40, U11/U12 small nuclear ribonucleoprotein 65 kDa protein

All UniProt accessions (5): E9PPV2, H0YE07, H0YEB8, Q96LT9, X6RLP6

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Component of the U11/U12 snRNPs that are part of the U12-type spliceosome. Found in a complex with m(7)G-capped U12 snRNA. Interacts with PDCD7.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in pancreas and kidney. Detected at lower levels in heart, brain, placenta, lung, liver, spleen, thymus, prostate, testis, ovary, small intestine, colon and leukocytes.

Disease relevance. Pituitary hormone deficiency, combined or isolated, 7 (CPHD7) [MIM:618160] An autosomal recessive deficiency of growth hormone characterized by severe postnatal growth failure, delayed bone age without bone dysplasia, and hypoplasia of the anterior pituitary. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96LT9-1	1	yes
Q96LT9-2	2

RefSeq proteins (1): NP_060089* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034147	RBM40_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR045164	RBM41/RNPC3	Family

Pfam: PF00076

UniProt features (30 total): helix 7, strand 5, region of interest 5, compositionally biased region 3, domain 2, modified residue 2, sequence variant 2, chain 1, splice variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3EGN	X-RAY DIFFRACTION	2.5
5OBN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LT9-F1	67.73	0.34

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 21, 108

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 144 (showing top): FISCHER_G1_S_CELL_CYCLE, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, FISCHER_DREAM_TARGETS, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, CUI_TCF21_TARGETS_2_DN, chr1p21, REACTOME_METABOLISM_OF_RNA, GOCC_SPLICEOSOMAL_COMPLEX, GOCC_RIBONUCLEOPROTEIN_COMPLEX, GEORGES_TARGETS_OF_MIR192_AND_MIR215, THUM_SYSTOLIC_HEART_FAILURE_DN

GO Biological Process (3): mRNA splicing, via spliceosome (GO:0000398), RNA splicing (GO:0008380), mRNA processing (GO:0006397)

GO Molecular Function (5): U12 snRNA binding (GO:0030626), pre-mRNA intronic binding (GO:0097157), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), U12-type spliceosomal complex (GO:0005689), spliceosomal complex (GO:0005681)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Splicing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
binding	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
snRNA binding	1
pre-mRNA binding	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
spliceosomal complex	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

1721 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNPC3	SNRNP48	Q6IEG0	809
RNPC3	ZCRB1	Q8TBF4	684
RNPC3	SNRNP35	Q16560	633
RNPC3	SNRNP25	Q9BV90	627
RNPC3	GHRHR	Q02643	610
RNPC3	IGHV3-15	A0A0B4J1V0	573
RNPC3	BAZ1B	Q9UIG0	566
RNPC3	ZRSR2	Q15696	551
RNPC3	EIF4H	Q15056	547
RNPC3	ZMAT5	Q9UDW3	542
RNPC3	GTF2I	P78347	526
RNPC3	PLAC8L1	A1L4L8	523
RNPC3	GH1	P01241	507
RNPC3	GEMIN5	Q8TEQ6	464
RNPC3	SNRNP70	P08621	452

IntAct

75 interactions, top by confidence:

A	B	Type	Score
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
ZRSR2	SF3B1	psi-mi:“MI:0914”(association)	0.730
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SNUPN	SNRPE	psi-mi:“MI:0914”(association)	0.640
ZCRB1	SF3B1	psi-mi:“MI:0914”(association)	0.640
RNPC3	NOLC1	psi-mi:“MI:0915”(physical association)	0.540
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
ZCRB1	DKC1	psi-mi:“MI:0914”(association)	0.530
ZMAT5	DENND4B	psi-mi:“MI:0914”(association)	0.530
SNRPE	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
SNRPF	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
SRPK2	RRP9	psi-mi:“MI:0914”(association)	0.530
SNRPB2	CDC40	psi-mi:“MI:0914”(association)	0.530
RNPC3	ACTC1	psi-mi:“MI:0915”(physical association)	0.400
RNPC3	P4HA1	psi-mi:“MI:0915”(physical association)	0.400
RNPC3	E7	psi-mi:“MI:0915”(physical association)	0.370
RNPC3	SMAD2	psi-mi:“MI:0915”(physical association)	0.370
Srp72		psi-mi:“MI:0914”(association)	0.350

BioGRID (67): RNPC3 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS), RNPC3 (Synthetic Lethality), RNPC3 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS), RNPC3 (Affinity Capture-MS)

ESM2 similar proteins: A4FVJ7, A6QPE1, E7F7X0, F1Q8J0, O43683, O60566, P92204, Q08AZ1, Q0VBD2, Q32NQ8, Q3MHP0, Q3UZ01, Q4G055, Q4R707, Q561R3, Q5F3D1, Q5HZN1, Q5R4U2, Q5R6C7, Q5R789, Q5RL73, Q5SPR8, Q5ZIX8, Q6DD45, Q6DE94, Q6DJS0, Q6GQJ2, Q6IE81, Q6IRB8, Q6NZY4, Q6P2L6, Q6XV80, Q6ZPI0, Q76FK4, Q7L590, Q7ZVP1, Q7ZXG4, Q801E2, Q8JZV4, Q8K298

Diamond homologs: F1Q8J0, Q3MHP0, Q3UZ01, Q4G055, Q5R6C7, Q8JZV4, Q8RWV8, Q96IZ5, Q96LT9, A2Y0J7, B8AM21, O22922, O74968, P08579, P09012, P32605, P40567, P43332, P45429, P59708, Q06AA4, Q0DKM4, Q10MR0, Q18409, Q2KIR1, Q39244, Q54J05, Q62189, Q7LL14, Q7ZWA3, Q8H1S6, Q8ITY4, Q9CQI7, Q9FMP4, Q9Y3B4, A5A6M3, A6NDE4, A6NEQ0, D4AE41, O04319

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metabolism of non-coding RNA	8	94.0×	1e-13
mRNA Splicing - Minor Pathway	18	74.6×	1e-28
mRNA Splicing	20	40.7×	2e-26
mRNA Polyadenylation	23	37.4×	3e-29
snRNP Assembly	9	35.2×	4e-11
CHD1 and CHD2 subfamily	17	34.2×	5e-21
Processing of Capped Intron-Containing Pre-mRNA	21	31.9×	2e-25
SARS-CoV-2 modulates host translation machinery	7	29.0×	4e-08

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	14	136.5×	2e-25
spliceosomal complex assembly	8	75.2×	5e-12
spliceosomal snRNP assembly	8	72.6×	6e-12
negative regulation of mRNA splicing, via spliceosome	5	59.8×	7e-07
RNA splicing, via transesterification reactions	5	48.8×	2e-06
mRNA splicing, via spliceosome	22	31.5×	2e-25
RNA splicing	22	30.3×	3e-25
mRNA processing	13	16.0×	5e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

100 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	1
Uncertain significance	72
Likely benign	9
Benign	4

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1064669	NM_017619.4(RNPC3):c.613C>T (p.Arg205Ter)	Pathogenic
1064670	NM_017619.4(RNPC3):c.624+1G>T	Pathogenic
1064671	NM_017619.4(RNPC3):c.1421del (p.Pro474fs)	Pathogenic
1064672	NM_017619.4(RNPC3):c.1449A>T (p.Leu483Phe)	Pathogenic
1319998	NM_017619.4(RNPC3):c.259C>T (p.Gln87Ter)	Pathogenic
1319999	NM_017619.4(RNPC3):c.443G>C (p.Gly148Ala)	Pathogenic
1320000	NM_017619.4(RNPC3):c.261dup (p.Leu88fs)	Pathogenic
1320001	NM_017619.4(RNPC3):c.1228T>G (p.Phe410Val)	Pathogenic
587367	NM_017619.4(RNPC3):c.1420C>A (p.Pro474Thr)	Pathogenic
587368	NM_017619.4(RNPC3):c.1504C>T (p.Arg502Ter)	Pathogenic
3062137	NM_017619.4(RNPC3):c.894-2A>G	Likely pathogenic

SpliceAI

2643 predictions. Top by Δscore:

Variant	Effect	Δscore
1:103526249:A:G	donor_gain	1.0000
1:103533731:A:AG	acceptor_gain	1.0000
1:103533731:AACT:A	acceptor_gain	1.0000
1:103533732:A:G	acceptor_gain	1.0000
1:103533734:T:A	acceptor_gain	1.0000
1:103534854:ATGGG:A	donor_loss	1.0000
1:103534855:TGGG:T	donor_loss	1.0000
1:103534856:GG:G	donor_gain	1.0000
1:103534856:GGGT:G	donor_loss	1.0000
1:103534857:GG:G	donor_gain	1.0000
1:103534857:GGT:G	donor_loss	1.0000
1:103534858:G:GG	donor_gain	1.0000
1:103534858:GTTAG:G	donor_loss	1.0000
1:103534859:T:A	donor_loss	1.0000
1:103535327:TAG:T	acceptor_loss	1.0000
1:103535328:A:AG	acceptor_gain	1.0000
1:103535328:AGGCT:A	acceptor_gain	1.0000
1:103535329:G:GA	acceptor_gain	1.0000
1:103535329:GGC:G	acceptor_gain	1.0000
1:103535329:GGCT:G	acceptor_gain	1.0000
1:103535329:GGCTG:G	acceptor_gain	1.0000
1:103535437:TACAG:T	donor_gain	1.0000
1:103535439:CAGG:C	donor_loss	1.0000
1:103535440:AG:A	donor_gain	1.0000
1:103535440:AGGTA:A	donor_loss	1.0000
1:103535441:GG:G	donor_gain	1.0000
1:103535442:G:GG	donor_gain	1.0000
1:103535442:GT:G	donor_loss	1.0000
1:103536124:A:G	acceptor_gain	1.0000
1:103537336:A:AG	acceptor_gain	1.0000

AlphaMissense

3395 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:103526162:T:A	V31D	1.000
1:103526210:T:C	L47P	1.000
1:103527705:C:A	A68D	1.000
1:103527711:C:A	A70D	1.000
1:103527735:C:A	A78D	1.000
1:103536136:T:C	L189P	1.000
1:103546981:T:C	L436P	1.000
1:103550973:T:C	M465T	1.000
1:103550987:T:C	F470L	1.000
1:103550988:T:C	F470S	1.000
1:103550988:T:G	F470C	1.000
1:103550989:C:A	F470L	1.000
1:103550989:C:G	F470L	1.000
1:103551072:T:A	V498D	1.000
1:103551728:C:A	A501D	1.000
1:103526156:T:A	L29H	0.999
1:103526156:T:C	L29P	0.999
1:103526171:T:A	L34Q	0.999
1:103526171:T:C	L34P	0.999
1:103526183:T:C	L38P	0.999
1:103526210:T:A	L47Q	0.999
1:103526225:C:A	A52D	0.999
1:103527704:G:C	A68P	0.999
1:103527716:T:C	F72L	0.999
1:103527717:T:C	F72S	0.999
1:103527718:C:A	F72L	0.999
1:103527718:C:G	F72L	0.999
1:103533752:T:C	L85P	0.999
1:103533754:C:G	H86D	0.999
1:103533782:T:C	L95S	0.999

dbSNP variants (sampled 300 via entrez): RS1000236203 (1:103545753 A>T), RS1000245960 (1:103546154 C>G), RS1000284333 (1:103525216 G>A,T), RS1000329519 (1:103531550 A>G), RS1000334564 (1:103527483 G>C), RS1000437625 (1:103538842 A>G,T), RS1000564417 (1:103552074 C>A,T), RS1000578915 (1:103538571 A>G), RS1000686323 (1:103545311 C>G), RS1000789293 (1:103527881 T>A), RS1000809350 (1:103552269 A>C,G), RS1000912995 (1:103552333 G>C), RS1000976450 (1:103539080 C>T), RS1001258378 (1:103526643 A>G), RS1001322226 (1:103539315 G>A)

Disease associations

OMIM: gene MIM:618016 | disease phenotypes: MIM:618160

GenCC curated gene-disease

Disease	Classification	Inheritance
isolated growth hormone deficiency, type 5	Definitive	Autosomal recessive
isolated growth hormone deficiency type IA	Supportive	Autosomal recessive

Mondo (2): isolated growth hormone deficiency, type 5 (MONDO:0032569), isolated growth hormone deficiency type IA (MONDO:0009876)

Orphanet (0):

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000824	Decreased response to growth hormone stimulation test
HP:0001956	Truncal obesity
HP:0002007	Frontal bossing
HP:0002750	Delayed skeletal maturation
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0008897	Postnatal growth retardation
HP:0010627	Anterior pituitary hypoplasia
HP:0012743	Abdominal obesity

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537404	Pituitary dwarfism 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, decreases expression	4
bisphenol A	decreases expression, increases methylation	3
trichostatin A	decreases expression, affects cotreatment	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
deguelin	decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Leflunomide	decreases expression	1
Caffeine	decreases phosphorylation	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Quercetin	decreases phosphorylation	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	increases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.