DHX38

Summary

DHX38 (DEAH-box helicase 38, HGNC:17211) is a protein-coding gene on chromosome 16q22.2, encoding Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (Q92620). Probable ATP-binding RNA helicase. It is a selective cancer dependency (DepMap: 45.1% of cell lines).

DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. The protein encoded by this gene is a member of the DEAD/H box family of splicing factors. This protein resembles yeast Prp16 more closely than other DEAD/H family members. It is an ATPase and essential for the catalytic step II in pre-mRNA splicing process.

Source: NCBI Gene 9785 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa 84 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 19
• Clinical variants (ClinVar): 930 total — 4 likely-pathogenic
• Phenotypes (HPO): 38
• Cancer dependency (DepMap): dependent in 45.1% of screened cell lines
• MANE Select transcript: NM_014003

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17211
Approved symbol	DHX38
Name	DEAH-box helicase 38
Location	16q22.2
Locus type	gene with protein product
Status	Approved
Aliases	Prp16, KIAA0224, hPrp16, PRPF16
Ensembl gene	ENSG00000140829
Ensembl biotype	protein_coding
OMIM	605584
Entrez	9785

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 13 protein_coding, 7 retained_intron, 1 nonsense_mediated_decay

ENST00000268482, ENST00000562774, ENST00000563650, ENST00000563819, ENST00000564307, ENST00000564622, ENST00000566329, ENST00000566489, ENST00000566794, ENST00000567142, ENST00000567552, ENST00000569935, ENST00000569952, ENST00000579387, ENST00000904785, ENST00000904786, ENST00000904787, ENST00000904788, ENST00000904789, ENST00000924633, ENST00000971158

RefSeq mRNA: 1 — MANE Select: NM_014003 NM_014003

CCDS: CCDS10907

Canonical transcript exons

ENST00000268482 — 27 exons

Exon	Start	End
ENSE00000945215	72096139	72096480
ENSE00000945216	72096822	72097009
ENSE00000945221	72099732	72099887
ENSE00000945222	72100436	72100597
ENSE00000945223	72101086	72101193
ENSE00000945227	72103946	72104131
ENSE00000945228	72104486	72104626
ENSE00000945229	72105027	72105137
ENSE00000945230	72105232	72105348
ENSE00001890118	72112413	72112912
ENSE00002239591	72093847	72094051
ENSE00003497955	72099204	72099280
ENSE00003498969	72106005	72106117
ENSE00003547818	72108227	72108382
ENSE00003558153	72103074	72103211
ENSE00003567339	72097677	72097781
ENSE00003570942	72105517	72105624
ENSE00003593462	72107340	72107548
ENSE00003594490	72109415	72109510
ENSE00003601697	72110956	72111077
ENSE00003609810	72108473	72108607
ENSE00003620383	72107645	72107799
ENSE00003621652	72098645	72098792
ENSE00003630582	72101500	72101612
ENSE00003656181	72103602	72103788
ENSE00003669012	72108800	72108925
ENSE00003678394	72098927	72099045

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 97.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.3240 / max 325.6449, expressed in 1817 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154971	14.5472	1802
154969	10.5775	1781
154972	0.6306	214
154968	0.2891	123
154970	0.2796	79

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.88	gold quality
left ovary	UBERON:0002119	95.08	gold quality
right ovary	UBERON:0002118	94.92	gold quality
peripheral nervous system	UBERON:0000010	94.70	gold quality
tibial nerve	UBERON:0001323	94.70	gold quality
granulocyte	CL:0000094	94.66	gold quality
apex of heart	UBERON:0002098	94.64	gold quality
calcaneal tendon	UBERON:0003701	94.31	gold quality
body of uterus	UBERON:0009853	94.29	gold quality
skin of leg	UBERON:0001511	94.24	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.24	gold quality
endometrium epithelium	UBERON:0004811	94.07	gold quality
skin of abdomen	UBERON:0001416	94.02	gold quality
left uterine tube	UBERON:0001303	94.01	gold quality
ganglionic eminence	UBERON:0004023	93.89	gold quality
mucosa of stomach	UBERON:0001199	93.62	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.62	gold quality
metanephros cortex	UBERON:0010533	93.53	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.49	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.47	gold quality
spleen	UBERON:0002106	93.40	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.32	gold quality
left lobe of thyroid gland	UBERON:0001120	93.31	gold quality
lower esophagus	UBERON:0013473	93.31	gold quality
transverse colon	UBERON:0001157	93.21	gold quality
right uterine tube	UBERON:0001302	93.21	gold quality
right lobe of thyroid gland	UBERON:0001119	93.13	gold quality
endocervix	UBERON:0000458	93.12	gold quality
cerebellar hemisphere	UBERON:0002245	93.11	gold quality
lower esophagus mucosa	UBERON:0035834	93.11	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting DHX38, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-541-5P	98.24	67.77	1181
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-1245B-3P	98.01	68.91	1387
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-3159	97.94	66.79	1098
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-4258	90.68	62.19	164

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 45.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• DHX38 is the first pre-mRNA splicing gene that is putatively associated with autosomal-recessive inherited retinitis pigmentosa. (PMID:24737827)
• We identified a second deleterious DHX38 variant that segregates with arRP in two families, providing additional evidence that DHX38 is involved in RP etiology. DHX38 encodes for pre-mRNA splicing factor PRP16, which is important in catalyzing pre-mRNA splicing. (PMID:30208423)
• The splicing factor DHX38/PRP16 is required for ovarian clear cell carcinoma tumorigenesis, as revealed by a CRISPR-Cas9 screen. (PMID:34965029)
• Retinitis pigmentosa-linked mutation in DHX38 modulates its splicing activity. (PMID:35385551)
• DHX38 restricts chemoresistance by regulating the alternative pre-mRNA splicing of RELL2 in pancreatic ductal adenocarcinoma. (PMID:37506056)
• DHX38 enhances proliferation, metastasis, and EMT progression in NSCLC through the G3BP1-mediated MAPK pathway. (PMID:37931691)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dhx38	ENSDARG00000100013
mus_musculus	Dhx38	ENSMUSG00000037993
rattus_norvegicus	Dhx38	ENSRNOG00000014619
drosophila_melanogaster	Prp16	FBGN0026713
caenorhabditis_elegans		WBGENE00003389

Paralogs (18): DHX33 (ENSG00000005100), YTHDC2 (ENSG00000047188), DHX29 (ENSG00000067248), DHX8 (ENSG00000067596), DHX32 (ENSG00000089876), DHX35 (ENSG00000101452), DHX40 (ENSG00000108406), DHX15 (ENSG00000109606), HELB (ENSG00000127311), DHX30 (ENSG00000132153), DHX34 (ENSG00000134815), DHX9 (ENSG00000135829), DQX1 (ENSG00000144045), DHX37 (ENSG00000150990), TDRD9 (ENSG00000156414), DHX57 (ENSG00000163214), DHX36 (ENSG00000174953), DHX16 (ENSG00000204560)

Protein

Protein identifiers

Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 — Q92620 (reviewed: Q92620)

Alternative names: ATP-dependent RNA helicase DHX38, DEAH box protein 38

All UniProt accessions (7): Q92620, H3BMS7, H3BQT9, H3BV01, J3KRT1, J3KSA8, J3KTG2

UniProt curated annotations — full annotation on UniProt →

Function. Probable ATP-binding RNA helicase. Involved in pre-mRNA splicing as component of the spliceosome.

Subunit / interactions. Identified in the spliceosome C complex.

Subcellular location. Nucleus.

Disease relevance. Retinitis pigmentosa 84 (RP84) [MIM:618220] A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP84 is an autosomal recessive, early onset form characterized by night blindness by age 4 and complete blindness by age 8. Funduscopy shows severely attenuated retinal vessels, severe macular atrophy, and prominent and deep macular colobomas lacking neuroretinal tissue. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the DEAD box helicase family. DEAH subfamily. PRP16 sub-subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q92620-1	1	yes
Q92620-2	2

RefSeq proteins (1): NP_054722* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001650	Helicase_C-like	Domain
IPR002464	DNA/RNA_helicase_DEAH_CS	Conserved_site
IPR007502	Helicase-assoc_dom	Domain
IPR011545	DEAD/DEAH_box_helicase_dom	Domain
IPR011709	DEAD-box_helicase_OB_fold	Domain
IPR014001	Helicase_ATP-bd	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR048333	HA2_WH	Domain

Pfam: PF00270, PF00271, PF04408, PF07717, PF21010

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (34 total): compositionally biased region 8, modified residue 7, cross-link 4, sequence variant 3, domain 2, turn 2, region of interest 2, initiator methionine 1, chain 1, binding site 1, splice variant 1, helix 1, short sequence motif 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6ZYM	ELECTRON MICROSCOPY	3.4
8I0W	ELECTRON MICROSCOPY	3.4
5YZG	ELECTRON MICROSCOPY	4.1
7A5P	ELECTRON MICROSCOPY	5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92620-F1	67.82	0.16

Functional residue map

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

Ligand- & substrate-binding residues (1): 555–562

Post-translational modifications (11): 2, 56, 117, 199, 224, 260, 1194, 482, 483, 504, 1166

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72187	mRNA 3’-end processing
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-73856	RNA Polymerase II Transcription Termination

MSigDB gene sets: 206 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8_TCELL_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, chr16q22, MORF_SNRP70, MORF_UBE2I, CHX10_01, MORF_TERF1, MORF_RAF1, MORF_CTBP1, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, JIANG_TIP30_TARGETS_DN, REACTOME_MRNA_SPLICING

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

GO Molecular Function (11): RNA binding (GO:0003723), RNA helicase activity (GO:0003724), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), 3’-5’ RNA helicase activity (GO:0034458), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), helicase activity (GO:0004386), protein binding (GO:0005515), ATP-dependent activity, acting on RNA (GO:0008186), hydrolase activity (GO:0016787)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), membrane (GO:0016020), catalytic step 2 spliceosome (GO:0071013), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Transport of Mature Transcript to Cytoplasm	1
mRNA Splicing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Dengue Virus Infection	1
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	3
RNA processing	2
binding	2
cellular anatomical structure	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
helicase activity	1
ATP-dependent activity, acting on RNA	1
catalytic activity, acting on RNA	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
RNA helicase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1
catalytic complex	1
protein-containing complex	1

Protein interactions and networks

STRING

3110 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHX38	CDC40	O60508	991
DHX38	PRPF18	Q99633	990
DHX38	DDX46	Q7L014	976
DHX38	DDX23	Q9BUQ8	966
DHX38	SLU7	O95391	921
DHX38	SNRNP200	O75643	907
DHX38	CWC25	Q9NXE8	860
DHX38	YJU2	Q9BW85	847
DHX38	EFTUD2	Q15029	730
DHX38	XAB2	Q9HCS7	716
DHX38	RNF113A	O15541	690
DHX38	PRPF3	O43395	690
DHX38	CWC27	Q6UX04	686
DHX38	CWC22	Q9HCG8	665
DHX38	SF3B1	O75533	663

IntAct

110 interactions, top by confidence:

A	B	Type	Score
SNRNP40	SNRNP200	psi-mi:“MI:0914”(association)	0.810
PPP4R2	TIPRL	psi-mi:“MI:0914”(association)	0.800
CD2BP2	SNRNP200	psi-mi:“MI:0914”(association)	0.800
PPP4C	TCP1	psi-mi:“MI:0914”(association)	0.730
DHX38	PPP4C	psi-mi:“MI:0914”(association)	0.730
DHX38	NUDCD1	psi-mi:“MI:0915”(physical association)	0.710
KHDRBS1	KHDRBS3	psi-mi:“MI:0914”(association)	0.670
PPP4C	SUPT5H	psi-mi:“MI:0914”(association)	0.640
DHX38	PPP4R3A	psi-mi:“MI:0914”(association)	0.640
DHX38	DHX16	psi-mi:“MI:0914”(association)	0.630
DHX38	DHX16	psi-mi:“MI:0915”(physical association)	0.630
PPP4R2	SF3B1	psi-mi:“MI:0914”(association)	0.570
PPP4R2	SF3B1	psi-mi:“MI:2364”(proximity)	0.570
C7orf25	RANBP2	psi-mi:“MI:0915”(physical association)	0.540
FAM177A1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
LDLRAD4	WWP2	psi-mi:“MI:0914”(association)	0.530
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
DHX38	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
GPKOW	DHX38	psi-mi:“MI:0915”(physical association)	0.510
DHX38	RBM10	psi-mi:“MI:0915”(physical association)	0.510
DHX38	GPKOW	psi-mi:“MI:0915”(physical association)	0.510
DHX38	CSNK2A1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
DHX38	PDIA4	psi-mi:“MI:0915”(physical association)	0.400
Prpf8		psi-mi:“MI:0915”(physical association)	0.400
WBP4	DHX38	psi-mi:“MI:0915”(physical association)	0.370
U2AF1	DHX38	psi-mi:“MI:0915”(physical association)	0.370
DHX38	MFAP1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (229): DHX38 (Affinity Capture-RNA), DHX38 (Affinity Capture-RNA), DHX38 (Affinity Capture-RNA), DHX38 (Affinity Capture-MS), DHX38 (Affinity Capture-MS), DHX38 (Affinity Capture-MS), DHX38 (Affinity Capture-MS), DHX38 (Affinity Capture-MS), DHX38 (Affinity Capture-MS), CLTC (Co-fractionation), DHX38 (Co-fractionation), DHX38 (Co-fractionation), DHX38 (Co-fractionation), PITHD1 (Co-fractionation), DHX38 (Affinity Capture-MS)

ESM2 similar proteins: A1Z9L3, A2A4P0, A2QIL2, A3KFM7, A3KMI0, B2RR83, B6ZLK2, D3ZA12, D4A2Z8, E9PZM4, F4IJV4, F4ILR7, F4JY24, F4K2E9, O14646, O14647, O18017, O42643, O45244, O60231, P24384, P34498, P40201, P93008, Q05B79, Q09530, Q10752, Q14562, Q17R09, Q38953, Q4TVV3, Q53RK8, Q54F05, Q5R746, Q5RAZ4, Q5ZI74, Q6P158, Q6P5D3, Q6PGC1, Q767K6

Diamond homologs: A1Z9L3, A2A4P0, B4GEU5, B4JT42, B4K5R2, B4RC48, D4A2Z8, F4HYJ7, F4IE66, F4IJV4, F4ILR7, F4IM84, F4JMJ3, F4JRJ6, F4K2E9, F4KGU4, O17438, O22243, O22899, O35286, O42643, O42945, O43143, O45244, O46072, O51767, O60114, O60231, O70133, O94536, P0C7L7, P0CE10, P15938, P20095, P24384, P34305, P34498, P36009, P37024, P43329

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 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
mRNA 3’-end processing	6	13.4×	4e-04
mRNA Splicing - Minor Pathway	5	12.7×	3e-03
mRNA Splicing - Major Pathway	19	11.8×	7e-13
mRNA Splicing	9	11.2×	1e-05
Transport of Mature mRNA derived from an Intron-Containing Transcript	6	10.4×	2e-03
Processing of Capped Intron-Containing Pre-mRNA	11	10.3×	2e-06
mRNA Polyadenylation	10	10.0×	8e-06
Dengue Virus-Host Interactions	18	9.3×	1e-10

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	8	16.7×	5e-06
mRNA splicing, via spliceosome	16	12.5×	1e-10
RNA splicing	15	11.3×	2e-09
mRNA processing	13	8.8×	7e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	4
Uncertain significance	464
Likely benign	398
Benign	29

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3028418	NM_014003.4(DHX38):c.601C>T (p.Arg201Ter)	Likely pathogenic
3028424	NM_014003.4(DHX38):c.1879T>A (p.Tyr627Asn)	Likely pathogenic
592160	NM_014003.4(DHX38):c.971G>A (p.Arg324Gln)	Likely pathogenic
812307	NM_014003.4(DHX38):c.2329C>T (p.Pro777Ser)	Likely pathogenic

SpliceAI

3256 predictions. Top by Δscore:

Variant	Effect	Δscore
16:72096137:A:AG	acceptor_gain	1.0000
16:72096137:A:AT	acceptor_loss	1.0000
16:72096138:G:GG	acceptor_gain	1.0000
16:72096138:GA:G	acceptor_gain	1.0000
16:72096138:GAGA:G	acceptor_gain	1.0000
16:72096138:GAGAA:G	acceptor_gain	1.0000
16:72096437:G:GT	donor_gain	1.0000
16:72096473:A:T	donor_gain	1.0000
16:72096476:GACAG:G	donor_gain	1.0000
16:72096478:CAGG:C	donor_loss	1.0000
16:72096481:G:GC	donor_loss	1.0000
16:72096482:T:G	donor_loss	1.0000
16:72096817:TTCAG:T	acceptor_loss	1.0000
16:72096820:A:AG	acceptor_gain	1.0000
16:72096820:A:C	acceptor_loss	1.0000
16:72096821:G:GA	acceptor_gain	1.0000
16:72096821:GA:G	acceptor_gain	1.0000
16:72096821:GAC:G	acceptor_gain	1.0000
16:72096821:GACA:G	acceptor_gain	1.0000
16:72096821:GACAT:G	acceptor_gain	1.0000
16:72097007:GAG:G	donor_gain	1.0000
16:72097008:AGGT:A	donor_loss	1.0000
16:72097010:G:GG	donor_gain	1.0000
16:72097010:GTA:G	donor_loss	1.0000
16:72097011:T:G	donor_loss	1.0000
16:72098637:T:TA	acceptor_gain	1.0000
16:72099198:CTCCA:C	acceptor_loss	1.0000
16:72099202:A:AG	acceptor_gain	1.0000
16:72099202:AG:A	acceptor_gain	1.0000
16:72099202:AGG:A	acceptor_loss	1.0000

AlphaMissense

8081 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:72099742:G:C	R324P	1.000
16:72099747:T:A	W326R	1.000
16:72099747:T:C	W326R	1.000
16:72099749:G:C	W326C	1.000
16:72099749:G:T	W326C	1.000
16:72100446:G:C	R376P	1.000
16:72100448:T:A	W377R	1.000
16:72100448:T:C	W377R	1.000
16:72100449:G:C	W377S	1.000
16:72100450:G:C	W377C	1.000
16:72100450:G:T	W377C	1.000
16:72100461:G:C	R381P	1.000
16:72100464:T:C	M382T	1.000
16:72100467:T:C	L383P	1.000
16:72100472:A:C	S385R	1.000
16:72100474:T:A	S385R	1.000
16:72100474:T:G	S385R	1.000
16:72100475:G:T	G386W	1.000
16:72100565:T:C	F416L	1.000
16:72100567:T:A	F416L	1.000
16:72100567:T:G	F416L	1.000
16:72100569:T:C	L417P	1.000
16:72101119:T:C	S438P	1.000
16:72101186:G:C	R460P	1.000
16:72103169:T:C	L532P	1.000
16:72103627:G:A	G555R	1.000
16:72103627:G:C	G555R	1.000
16:72103627:G:T	G555W	1.000
16:72103628:G:A	G555E	1.000
16:72103636:G:T	G558W	1.000

dbSNP variants (sampled 300 via entrez): RS1000169774 (16:72107012 T>C), RS1000379312 (16:72091909 C>T), RS1000519009 (16:72092906 G>A), RS1000570044 (16:72092768 G>T), RS1000862160 (16:72097098 C>T), RS1000986196 (16:72093062 C>A), RS1001084950 (16:72098291 G>T), RS1001233154 (16:72103497 C>A), RS1001249964 (16:72092810 A>G,T), RS1001296158 (16:72111597 T>C), RS1002010864 (16:72095803 C>T), RS1002041898 (16:72096058 C>T), RS1002484205 (16:72107077 G>A), RS1002749165 (16:72112812 T>G), RS1002938728 (16:72109991 A>G,T)

Disease associations

OMIM: gene MIM:605584 | disease phenotypes: MIM:618220, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 84	Strong	Autosomal recessive
retinitis pigmentosa	Supportive	Autosomal dominant

Mondo (3): retinitis pigmentosa 84 (MONDO:0032604), inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa (MONDO:0019200)

Orphanet (2): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0001116	Macular pseudocoloboma
HP:0007401	Macular atrophy
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007787	Posterior subcapsular cataract
HP:0007843	Attenuation of retinal blood vessels
HP:0007994	Peripheral visual field loss
HP:0008046	Abnormal retinal vascular morphology

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000759_13	LDL cholesterol	2.000000e-22
GCST000760_22	Cholesterol, total	3.000000e-24
GCST001639_4	Metabolite levels	1.000000e-36
GCST002896_11	Cholesterol, total	3.000000e-23
GCST002898_10	LDL cholesterol	2.000000e-20
GCST005195_143	Coronary artery disease	3.000000e-11
GCST005196_18	Coronary artery disease	3.000000e-11
GCST005839_18	Depression	3.000000e-08
GCST007931_23	Medication use (HMG CoA reductase inhibitors)	3.000000e-19
GCST008972_206	Urate levels	2.000000e-09
GCST009159_12	Blood protein levels	1.000000e-10
GCST009240_372	Serum metabolite levels (CMS)	1.000000e-10
GCST009240_413	Serum metabolite levels (CMS)	4.000000e-10
GCST009600_70	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	3.000000e-09
GCST010083_205	Hemoglobin levels	2.000000e-08
GCST010083_65	Hemoglobin levels	7.000000e-09
GCST90002383_248	Hematocrit	3.000000e-20
GCST90002384_366	Hemoglobin	7.000000e-25
GCST90002403_682	Red blood cell count	3.000000e-25

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004723	coronary artery calcification
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004531	urate measurement
EFO:0004747	protein measurement
EFO:0004813	alpha globulin measurement
EFO:0004509	hemoglobin measurement
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	increases expression, decreases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	affects sumoylation	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
sodium arsenite	increases expression	1
tetrabromobisphenol A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Clozapine	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Haloperidol	decreases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases phosphorylation	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tamoxifen	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa