DHX37

Summary

DHX37 (DEAH-box helicase 37, HGNC:17210) is a protein-coding gene on chromosome 12q24.31, encoding Probable ATP-dependent RNA helicase DHX37 (Q8IY37). ATP-binding RNA helicase that plays a role in maturation of the small ribosomal subunit in ribosome biogenesis. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

This gene encodes a DEAD box protein. 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.

Source: NCBI Gene 57647 — RefSeq curated summary.

At a glance

• Gene–disease (curated): 46,XY sex reversal 11 (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 646 total — 4 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 88
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_032656

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17210
Approved symbol	DHX37
Name	DEAH-box helicase 37
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1517, MGC4322, MGC2695, Dhr1
Ensembl gene	ENSG00000150990
Ensembl biotype	protein_coding
OMIM	617362
Entrez	57647

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 retained_intron

ENST00000308736, ENST00000507267, ENST00000542400, ENST00000543962, ENST00000544745, ENST00000679875, ENST00000880032, ENST00000880033, ENST00000921756

RefSeq mRNA: 1 — MANE Select: NM_032656 NM_032656

CCDS: CCDS9261

Canonical transcript exons

ENST00000308736 — 27 exons

Exon	Start	End
ENSE00001257078	124988917	124989131
ENSE00002238426	124946826	124947887
ENSE00003485491	124971302	124971415
ENSE00003485963	124949986	124950059
ENSE00003492450	124957029	124957135
ENSE00003498255	124980490	124980838
ENSE00003499189	124982511	124982623
ENSE00003507726	124964930	124965006
ENSE00003514517	124956691	124956879
ENSE00003519117	124968867	124968968
ENSE00003522762	124975419	124975511
ENSE00003527637	124965668	124965812
ENSE00003536994	124966793	124966878
ENSE00003539319	124948084	124948181
ENSE00003565656	124968534	124968648
ENSE00003574980	124952398	124952570
ENSE00003576505	124950149	124950243
ENSE00003579966	124954087	124954211
ENSE00003588958	124972503	124972599
ENSE00003594562	124967123	124967218
ENSE00003609562	124960312	124960423
ENSE00003613818	124964394	124964626
ENSE00003630076	124950690	124950804
ENSE00003630597	124950413	124950550
ENSE00003643088	124953880	124953996
ENSE00003667086	124977342	124977490
ENSE00003669798	124986096	124986265

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 96.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.4665 / max 265.8441, expressed in 1809 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134066	19.5729	1809
134065	0.8936	408

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	96.70	silver quality
tendon of biceps brachii	UBERON:0008188	96.21	silver quality
medial globus pallidus	UBERON:0002477	88.57	silver quality
sural nerve	UBERON:0015488	87.16	gold quality
upper arm skin	UBERON:0004263	86.78	silver quality
globus pallidus	UBERON:0001875	86.43	silver quality
gastrocnemius	UBERON:0001388	85.16	gold quality
muscle of leg	UBERON:0001383	84.04	gold quality
vena cava	UBERON:0004087	83.57	gold quality
granulocyte	CL:0000094	83.31	gold quality
epithelial cell of pancreas	CL:0000083	82.63	silver quality
kidney epithelium	UBERON:0004819	81.81	silver quality
lower esophagus mucosa	UBERON:0035834	81.80	gold quality
skin of leg	UBERON:0001511	81.52	gold quality
mucosa of transverse colon	UBERON:0004991	81.42	gold quality
right ovary	UBERON:0002118	81.38	gold quality
stromal cell of endometrium	CL:0002255	81.34	gold quality
left ovary	UBERON:0002119	81.15	gold quality
apex of heart	UBERON:0002098	81.14	gold quality
parotid gland	UBERON:0001831	81.10	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.59	gold quality
ectocervix	UBERON:0012249	80.38	gold quality
body of pancreas	UBERON:0001150	80.20	gold quality
spleen	UBERON:0002106	80.16	gold quality
esophagus mucosa	UBERON:0002469	80.16	gold quality
vermiform appendix	UBERON:0001154	80.10	gold quality
skin of abdomen	UBERON:0001416	79.89	gold quality
body of uterus	UBERON:0009853	79.88	gold quality
trachea	UBERON:0003126	79.79	gold quality
nerve	UBERON:0001021	79.77	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting DHX37, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-6088	99.29	68.45	1284
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-4290	98.51	65.17	907
HSA-MIR-4691-3P	98.11	66.83	1204
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-637	97.91	64.05	1517
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-7154-3P	97.65	65.02	985
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-6736-3P	96.98	65.22	1342
HSA-MIR-490-5P	96.75	65.81	661
HSA-MIR-4652-5P	96.46	64.22	553

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• In 46,XY Gonadal dysgenesis, we identified four heterozygous missense rare variants, classified as pathogenic or likely pathogenic in the Asp-Glu-Ala-His-box (DHX) helicase 37 (DHX37) gene.Two variants were recurrent: p.Arg308Gln and p.Arg674Trp. The variants were specifically associated with embryonic testicular regression syndrome. DHX37 is a player in the complex cascade of male gonadal differentiation and maintenance. (PMID:31287541)
• Results identified heterozygous missense pathogenic variants involving DHX37 gene as a new cause of an autosomal dominant form of 46,XY DSD, including gonadal dysgenesis and testicular regression syndrome (TRS), showing that these conditions are part of a clinical spectrum. Some of the variants are clustered in two highly conserved functional domains. (PMID:31337883)
• Integrative Expression and Prognosis Analysis of DHX37 in Human Cancers by Data Mining. (PMID:33490273)
• DHX37 Impacts Prognosis of Hepatocellular Carcinoma and Lung Adenocarcinoma through Immune Infiltration. (PMID:33490290)
• Expanding DSD Phenotypes Associated with Variants in the DEAH-Box RNA Helicase DHX37. (PMID:34293745)
• RNA Helicase DHX37 Facilitates Liver Cancer Progression by Cooperating with PLRG1 to Drive Superenhancer-Mediated Transcription of Cyclin D1. (PMID:35290436)
• DHX37 and 46,XY DSD: A New Ribosomopathy? (PMID:35835064)
• DHX37 and the Implications in Disorders of Sex Development: An Update Review. (PMID:38142677)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dhx37	ENSDARG00000062612
mus_musculus	Dhx37	ENSMUSG00000029480
rattus_norvegicus	Dhx37	ENSRNOG00000022171
drosophila_melanogaster	kz	FBGN0001330
caenorhabditis_elegans		WBGENE00015525

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), DHX38 (ENSG00000140829), DQX1 (ENSG00000144045), TDRD9 (ENSG00000156414), DHX57 (ENSG00000163214), DHX36 (ENSG00000174953), DHX16 (ENSG00000204560)

Protein

Protein identifiers

Probable ATP-dependent RNA helicase DHX37 — Q8IY37 (reviewed: Q8IY37)

Alternative names: DEAH box protein 37

All UniProt accessions (2): Q8IY37, F5H3Y4

UniProt curated annotations — full annotation on UniProt →

Function. ATP-binding RNA helicase that plays a role in maturation of the small ribosomal subunit in ribosome biogenesis. Required for the release of the U3 snoRNP from pre-ribosomal particles. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Plays a role in early testis development. Probably also plays a role in brain development.

Subunit / interactions. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with UTP14A.

Subcellular location. Nucleus. Nucleolus. Cytoplasm. Nucleus membrane.

Tissue specificity. Expressed in the fallopian tube, ovary, uterus and testis. Also expressed in the brain.

Disease relevance. Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies (NEDBAVC) [MIM:618731] An autosomal recessive neurodevelopmental disorder characterized by severe developmental delay, impaired intellectual development, hypotonia, brain anomalies including cortical volume loss, corpus callosum dysgenesis and cerebellar hypoplasia, and variable dysmorphic features. Patients may have platyspondyly, scoliosis, and cardiac anomalies. The disease may be caused by variants affecting the gene represented in this entry. 46,XY sex reversal 11 (SRXY11) [MIM:273250] An autosomal dominant disorder of sex development. Affected individuals have a 46,XY karyotype and a genital phenotype that may range from predominantly female to predominantly male, including marked sex ambiguity. Approximately half of patients present with micropenis and bilateral or unilateral cryptorchidism, and half present with female-appearing or ambiguous external genitalia. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the DEAD box helicase family. DEAH subfamily.

RefSeq proteins (1): NP_116045* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001650	Helicase_C-like	Domain
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
IPR056371	DHX37-like_C	Domain

Pfam: PF00270, PF00271, PF04408, PF07717, PF21010, PF23362

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (43 total): sequence variant 23, compositionally biased region 7, region of interest 4, sequence conflict 3, domain 2, chain 1, binding site 1, mutagenesis site 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7MQA	ELECTRON MICROSCOPY	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IY37-F1	76.27	0.41

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): 275–282

Mutagenesis-validated functional residues (1):

Position	Phenotype
282	impairs the catalytic activity of the helicase.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol

MSigDB gene sets: 277 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_MATURATION_OF_SSU_RRNA, GOBP_RIBOSOME_ASSEMBLY, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_MATURATION_OF_SSU_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GOBP_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_ORGANELLE_ASSEMBLY, GCM_DDX11, GOBP_HEAD_DEVELOPMENT, GOBP_SEX_DIFFERENTIATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GCM_NF2

GO Biological Process (6): maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000462), brain development (GO:0007420), ribosome biogenesis (GO:0042254), ribosome assembly (GO:0042255), ribosomal small subunit biogenesis (GO:0042274), positive regulation of male gonad development (GO:2000020)

GO Molecular Function (10): RNA binding (GO:0003723), RNA helicase activity (GO:0003724), helicase activity (GO:0004386), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), U3 snoRNA binding (GO:0034511), nucleotide binding (GO:0000166), nucleic acid binding (GO:0003676), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (7): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), nuclear membrane (GO:0031965), small-subunit processome (GO:0032040), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
ribonucleoprotein complex biogenesis	2
ribosome biogenesis	2
ATP-dependent activity	2
binding	2
nuclear lumen	2
maturation of SSU-rRNA	1
central nervous system development	1
animal organ development	1
head development	1
membraneless organelle assembly	1
male gonad development	1
positive regulation of gonad development	1
regulation of male gonad development	1
nucleic acid binding	1
helicase activity	1
ATP-dependent activity, acting on RNA	1
catalytic activity, acting on RNA	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
snoRNA binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
nucleus	1
nuclear envelope	1
organelle membrane	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DHX37	DOCK1	Q14185	942
DHX37	DOCK4	Q8N1I0	902
DHX37	DOCK9	Q9BZ29	896
DHX37	DOCK11	Q5JSL3	892
DHX37	DOCK10	Q96BY6	892
DHX37	UTP14A	Q9BVJ6	743
DHX37	DOCK7	Q96N67	718
DHX37	DDX49	Q9Y6V7	670
DHX37	PDCD11	Q14690	664
DHX37	DDX47	Q9H0S4	642
DHX37	BUD23	O43709	613
DHX37	DHX8	Q14562	602
DHX37	DOCK2	Q92608	598
DHX37	DOCK5	Q9H7D0	597
DHX37	RRP9	O43818	594

IntAct

91 interactions, top by confidence:

A	B	Type	Score
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
RSBN1	SETD1A	psi-mi:“MI:0914”(association)	0.530
N	NOP56	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
UTP14A	DHX37	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RRP8	MAGEB2	psi-mi:“MI:0914”(association)	0.530
CBX6	ZBTB24	psi-mi:“MI:0914”(association)	0.530
PRR3	MRPS14	psi-mi:“MI:0914”(association)	0.530
LIN28B	ELAVL2	psi-mi:“MI:0914”(association)	0.530
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
PLXNA2	DHX37	psi-mi:“MI:0915”(physical association)	0.370
ATXN1	DHX37	psi-mi:“MI:0915”(physical association)	0.370
Naa50	WDR46	psi-mi:“MI:0914”(association)	0.350
NOP56	C12orf43	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
KDM5B	PLPBP	psi-mi:“MI:0914”(association)	0.350
ORF4a	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
rep	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
N	POLRMT	psi-mi:“MI:0914”(association)	0.350
BYSL	RPS3A	psi-mi:“MI:0914”(association)	0.350
DHX37	PARN	psi-mi:“MI:0914”(association)	0.350
SLX9	BUD23	psi-mi:“MI:0914”(association)	0.350
NPM1	RPS3A	psi-mi:“MI:0914”(association)	0.350
PSPC1	MCRIP1	psi-mi:“MI:0914”(association)	0.350
RPS11	SCAMP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (218): DHX37 (Two-hybrid), DHX37 (Two-hybrid), DHX37 (Two-hybrid), DHX37 (Affinity Capture-MS), DHX15 (Co-fractionation), DHX37 (Co-fractionation), DHX37 (Co-fractionation), NAT10 (Co-fractionation), POLR1C (Co-fractionation), RBM19 (Co-fractionation), RPS3A (Co-fractionation), DHX37 (Affinity Capture-RNA), DHX37 (Affinity Capture-MS), DHX37 (Affinity Capture-MS), DHX37 (Affinity Capture-MS)

ESM2 similar proteins: A0A3S7WQS5, A1CA18, A2R994, A4HAG7, A4I9M7, A4ZZ93, A5DB27, A5DTX8, A5KB67, A7AQ93, A8JAN3, B5RUN4, B6Q1T9, B8MR69, B8NDZ1, B9FK36, O46072, O76819, P06595, P14773, P53893, P60315, P84737, Q07422, Q381F9, Q38BU9, Q38CE9, Q4DC43, Q4DKF7, Q4DYL7, Q4DZ91, Q4PMC9, Q4Q3F0, Q4QDI6, Q4QH39, Q57WH1, Q580W5, Q5BB57, Q6CBI0, Q6FP07

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 114 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
Eukaryotic Translation Initiation	6	26.8×	1e-06
Cap-dependent Translation Initiation	6	26.8×	1e-06
SARS-CoV-1 modulates host translation machinery	6	26.8×	1e-06
Formation of the ternary complex, and subsequently, the 43S complex	8	25.0×	2e-08
rRNA modification in the nucleus and cytosol	9	24.4×	3e-09
Eukaryotic Translation Elongation	6	24.2×	2e-06
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S	6	23.6×	2e-06
rRNA processing in the nucleus and cytosol	10	23.3×	8e-10

GO biological processes:

GO term	Partners	Fold	FDR
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	5	32.7×	3e-05
ribosomal large subunit biogenesis	6	25.8×	1e-05
ribosomal small subunit biogenesis	11	24.3×	4e-10
cytoplasmic translation	11	19.8×	1e-09
rRNA processing	12	16.5×	1e-09
translation	12	12.0×	4e-08
mRNA processing	8	6.1×	3e-03
RNA splicing	7	6.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	10
Uncertain significance	336
Likely benign	191
Benign	61

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
804277	NM_032656.4(DHX37):c.1399C>T (p.Leu467=)	Pathogenic
869419	NM_032656.4(DHX37):c.911C>T (p.Thr304Met)	Pathogenic
869420	NM_032656.4(DHX37):c.923G>A (p.Arg308Gln)	Pathogenic
869422	NM_032656.4(DHX37):c.1784C>T (p.Ser595Phe)	Pathogenic
1298360	NM_032656.4(DHX37):c.1877C>T (p.Ser626Leu)	Likely pathogenic
1342471	NM_032656.4(DHX37):c.3217-1G>T	Likely pathogenic
2690942	NM_032656.4(DHX37):c.2762A>G (p.Gln921Arg)	Likely pathogenic
2690985	NM_032656.4(DHX37):c.2177dup (p.Thr727fs)	Likely pathogenic
2690986	NM_032656.4(DHX37):c.2698A>G (p.Asn900Asp)	Likely pathogenic
402139	NM_032656.4(DHX37):c.1257C>A (p.Asn419Lys)	Likely pathogenic
691929	NM_032656.4(DHX37):c.1145A>G (p.Asp382Gly)	Likely pathogenic
691930	NM_032656.4(DHX37):c.3281C>T (p.Thr1094Met)	Likely pathogenic
869421	NM_032656.4(DHX37):c.2020C>T (p.Arg674Trp)	Likely pathogenic
869423	NM_032656.4(DHX37):c.2021G>A (p.Arg674Gln)	Likely pathogenic

SpliceAI

3986 predictions. Top by Δscore:

Variant	Effect	Δscore
12:124947883:CAGGT:C	acceptor_gain	1.0000
12:124947888:C:CC	acceptor_gain	1.0000
12:124948080:TCA:T	donor_loss	1.0000
12:124948081:CAC:C	donor_loss	1.0000
12:124948082:A:AC	donor_gain	1.0000
12:124948083:C:CA	donor_gain	1.0000
12:124948083:CA:C	donor_gain	1.0000
12:124948083:CAT:C	donor_gain	1.0000
12:124948083:CATT:C	donor_gain	1.0000
12:124948083:CATTT:C	donor_gain	1.0000
12:124948099:T:TA	donor_gain	1.0000
12:124948177:GCAGC:G	acceptor_gain	1.0000
12:124948178:CAGC:C	acceptor_gain	1.0000
12:124948178:CAGCC:C	acceptor_gain	1.0000
12:124948179:AGC:A	acceptor_gain	1.0000
12:124948180:GC:G	acceptor_gain	1.0000
12:124948181:CC:C	acceptor_gain	1.0000
12:124948182:C:CA	acceptor_loss	1.0000
12:124948182:C:CC	acceptor_gain	1.0000
12:124948183:T:G	acceptor_loss	1.0000
12:124949980:CAGTA:C	donor_loss	1.0000
12:124949984:A:T	donor_loss	1.0000
12:124949985:CC:C	donor_loss	1.0000
12:124950057:GAC:G	acceptor_gain	1.0000
12:124950059:CCTGA:C	acceptor_loss	1.0000
12:124950060:C:CC	acceptor_gain	1.0000
12:124950060:CTGAT:C	acceptor_loss	1.0000
12:124950144:CCTA:C	donor_loss	1.0000
12:124950145:CTA:C	donor_loss	1.0000
12:124950147:A:AC	donor_gain	1.0000

AlphaMissense

7485 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:124964571:G:T	A623D	0.999
12:124964584:C:G	A619P	0.999
12:124975449:C:G	R317P	0.999
12:124975467:G:T	A311D	0.999
12:124975470:G:T	A310D	0.999
12:124964406:C:T	G678D	0.998
12:124964513:C:A	K642N	0.998
12:124964513:C:G	K642N	0.998
12:124964589:A:T	V617D	0.998
12:124968934:G:T	A409D	0.998
12:124977390:C:T	G280E	0.998
12:124977391:C:A	G280W	0.998
12:124964398:A:C	Y681D	0.997
12:124964426:T:A	R671S	0.997
12:124964426:T:G	R671S	0.997
12:124964427:C:G	R671T	0.997
12:124964438:C:A	Q667H	0.997
12:124964438:C:G	Q667H	0.997
12:124964474:G:C	F655L	0.997
12:124964474:G:T	F655L	0.997
12:124964476:A:G	F655L	0.997
12:124964523:C:T	G639E	0.997
12:124964583:G:T	A619D	0.997
12:124964964:A:G	L593P	0.997
12:124971372:G:T	A374D	0.997
12:124972522:A:G	L353P	0.997
12:124975468:C:G	A311P	0.997
12:124977388:T:G	K281Q	0.997
12:124977392:G:C	S279R	0.997
12:124977392:G:T	S279R	0.997

dbSNP variants (sampled 300 via entrez): RS1000134890 (12:124963043 G>C), RS1000171120 (12:124987138 T>A,C), RS1000365935 (12:124986442 G>A), RS1000376547 (12:124952842 C>G), RS1000409093 (12:124953046 A>T), RS1000450782 (12:124976464 C>A), RS1000538184 (12:124967068 G>A), RS1000563803 (12:124971737 C>T), RS1000795517 (12:124947942 C>T), RS1000830597 (12:124990547 G>A), RS1000831828 (12:124962024 T>A,C), RS1000863841 (12:124976606 G>A), RS1000916439 (12:124966910 T>C), RS1000946101 (12:124990387 G>A,T), RS1001148174 (12:124961674 G>A)

Disease associations

OMIM: gene MIM:617362 | disease phenotypes: MIM:618731, MIM:273250, MIM:120430

GenCC curated gene-disease

Disease	Classification	Inheritance
46,XY sex reversal 11	Strong	Autosomal dominant
neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies	Strong	Autosomal recessive
46,XY complete gonadal dysgenesis	Supportive	Autosomal dominant
46,XY partial gonadal dysgenesis	Supportive	Autosomal dominant
testicular regression syndrome	Supportive	Autosomal recessive

Mondo (9): neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies (MONDO:0032888), 46,XY sex reversal 11 (MONDO:8000015), disorder of sexual differentiation (MONDO:0002145), intellectual disability (MONDO:0001071), polymicrogyria (MONDO:0000087), coloboma of optic nerve (MONDO:0007354), 46,XY complete gonadal dysgenesis (MONDO:0010765), 46,XY partial gonadal dysgenesis (MONDO:0016674), (MONDO:0010107)

Orphanet (8): Testicular regression syndrome (Orphanet:983), Difference of sex development (Orphanet:90771), Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805), Male infertility with spermatogenesis disorder (Orphanet:399775), Morning glory disc anomaly (Orphanet:35737), Polymicrogyria (Orphanet:35981), Coloboma of optic disc (Orphanet:98947), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

88 total (30 of 88 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000022	Abnormal male internal genitalia morphology
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000030	Testicular gonadoblastoma
HP:0000037	Male pseudohermaphroditism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000045	Abnormal scrotum morphology
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000058	Abnormal labia morphology
HP:0000062	Ambiguous genitalia
HP:0000100	Nephrotic syndrome
HP:0000133	Gonadal dysgenesis
HP:0000142	Abnormal vagina morphology
HP:0000144	Decreased fertility
HP:0000147	Polycystic ovaries
HP:0000149	Ovarian gonadoblastoma
HP:0000150	Gonadoblastoma
HP:0000151	Aplasia of the uterus
HP:0000252	Microcephaly
HP:0000271	Abnormality of the face
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000324	Facial asymmetry
HP:0000411	Protruding ear
HP:0000463	Anteverted nares

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005161_1	Insulin levels in response to oral glucose tolerance test (120 minutes)	3.000000e-06
GCST008162_29	Hip circumference	4.000000e-06
GCST010242_383	HDL cholesterol levels	4.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004307	glucose tolerance test
EFO:0004467	insulin measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D012734	Disorders of Sex Development	C12.050.351.875.253; C12.200.706.316; C12.800.316; C16.131.939.316; C19.391.119
D006061	Gonadal Dysgenesis, 46,XY	C12.050.351.875.253.096.687; C12.050.351.875.253.309.388; C12.200.706.316.096.687; C12.200.706.316.309.388; C12.800.316.096.687; C12.800.316.309.388; C16.131.939.316.096.687; C16.131.939.316.309.388; C19.391.119.096.687; C19.391.119.309.388
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065706	Polymicrogyria	C10.500.507.500.500; C16.131.666.507.500.500
C537770	Anorchia (supp.)
C535970	Coloboma of optic nerve (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Temozolomide	affects response to substance, increases expression	2
bisphenol F	affects cotreatment, decreases expression	1
ginger extract	affects cotreatment, affects expression, increases abundance	1
dicrotophos	increases expression	1
chloroacetaldehyde	increases expression	1
bisphenol A	affects cotreatment, affects expression, increases abundance	1
deoxynivalenol	increases expression	1
benzo(e)pyrene	increases methylation	1
nivalenol	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
1-(2-trifluoromethoxyphenyl)-2-nitroethanone	increases expression	1
Sunitinib	increases expression	1
Cidofovir	decreases expression	1
Acrolein	increases oxidation, affects cotreatment	1
Air Pollutants	increases expression	1
Benzo(a)pyrene	increases methylation	1
Carmustine	affects response to substance	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Clodronic Acid	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Ibuprofen	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT03718234	PHASE1	COMPLETED	Subcutaneous Hydrocortisone Children With Congenital Adrenal Hyperplasia
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT00485186	Not specified	WITHDRAWN	Gene Polymorphisms Influencing Steroid Synthesis and Action
NCT01875640	Not specified	COMPLETED	Decision Support for Parents Receiving Information About Child’s Rare Disease
NCT02784184	Not specified	UNKNOWN	COPENHAGEN Minipuberty Study
NCT03102554	Not specified	ENROLLING_BY_INVITATION	Genetics of Differences of Sex Development and Hypospadias
NCT03283852	Not specified	RECRUITING	Identifying New Genetic Causes to Development Disorders
NCT04195490	Not specified	UNKNOWN	Evaluation of Outcomes of Feminizing Genitoplasty in Children With Disorders of Sex Development
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT04717349	Not specified	RECRUITING	Data Collection Study of Pediatric and Adolescent Gynecology Conditions
NCT05058781	Not specified	RECRUITING	Minipuberty in Infants Born With Potential Hypogonadism Hypogonadotrope
NCT06692049	Not specified	RECRUITING	Gonadal Tissue Cryopreservation for Fertility Preservation in Children with a Disorder of Sex Development
NCT06989593	Not specified	RECRUITING	Breaking Silence Through Story: A Narrative Medicine Intervention for Parents of Children With Urogenital Conditions
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study