SNF8

Summary

SNF8 (SNF8 subunit of ESCRT-II, HGNC:17028) is a protein-coding gene on chromosome 17q21.32, encoding Vacuolar-sorting protein SNF8 (Q96H20). Component of the endosomal sorting complex required for transport II (ESCRT-II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs, and plays a role in autophagy. It is a common-essential gene (DepMap: required in 95.5% of cancer cell lines).

The protein encoded by this gene is a component of the endosomal sorting complex required for transport II (ESCRT-II), which regulates the movement of ubiquitinylated transmembrane proteins to the lysosome for degradation. This complex also interacts with the RNA polymerase II elongation factor (ELL) to overcome the repressive effects of ELL on RNA polymerase II activity. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 11267 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy 115 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 47 total — 6 pathogenic
• Phenotypes (HPO): 30
• Cancer dependency (DepMap): dependent in 95.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_007241

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17028
Approved symbol	SNF8
Name	SNF8 subunit of ESCRT-II
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Aliases	EAP30, VPS22, Dot3
Ensembl gene	ENSG00000159210
Ensembl biotype	protein_coding
OMIM	610904
Entrez	11267

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 9 protein_coding, 7 retained_intron, 7 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000290330, ENST00000502492, ENST00000504000, ENST00000506104, ENST00000507302, ENST00000509989, ENST00000509995, ENST00000510195, ENST00000510558, ENST00000511214, ENST00000512243, ENST00000514089, ENST00000514929, ENST00000515174, ENST00000515572, ENST00000573795, ENST00000576353, ENST00000856245, ENST00000856246, ENST00000930403, ENST00000930404, ENST00000930405, ENST00000930406, ENST00000956813

RefSeq mRNA: 4 — MANE Select: NM_007241 NM_001317192, NM_001317193, NM_001317194, NM_007241

CCDS: CCDS11541, CCDS82156

Canonical transcript exons

ENST00000502492 — 8 exons

Exon	Start	End
ENSE00002025779	48929316	48930612
ENSE00002072013	48944681	48944842
ENSE00003506496	48943925	48943975
ENSE00003511434	48937020	48937124
ENSE00003541096	48933205	48933346
ENSE00003593713	48936170	48936242
ENSE00003627046	48931643	48931717
ENSE00003628912	48940924	48941062

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 97.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.6490 / max 196.4041, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166769	43.5885	1825
166768	0.0604	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.87	gold quality
mucosa of transverse colon	UBERON:0004991	97.49	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.25	gold quality
lower esophagus	UBERON:0013473	97.23	gold quality
mucosa of stomach	UBERON:0001199	97.17	gold quality
stromal cell of endometrium	CL:0002255	97.13	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.08	gold quality
left coronary artery	UBERON:0001626	97.01	gold quality
ganglionic eminence	UBERON:0004023	96.97	gold quality
right atrium auricular region	UBERON:0006631	96.97	gold quality
right adrenal gland	UBERON:0001233	96.93	gold quality
popliteal artery	UBERON:0002250	96.91	gold quality
tibial artery	UBERON:0007610	96.91	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.91	gold quality
body of stomach	UBERON:0001161	96.88	gold quality
left adrenal gland	UBERON:0001234	96.87	gold quality
monocyte	CL:0000576	96.84	gold quality
aorta	UBERON:0000947	96.81	gold quality
left adrenal gland cortex	UBERON:0035825	96.81	gold quality
ascending aorta	UBERON:0001496	96.80	gold quality
thoracic aorta	UBERON:0001515	96.79	gold quality
granulocyte	CL:0000094	96.78	gold quality
right coronary artery	UBERON:0001625	96.76	gold quality
right adrenal gland cortex	UBERON:0035827	96.74	gold quality
right lobe of thyroid gland	UBERON:0001119	96.72	gold quality
heart left ventricle	UBERON:0002084	96.71	gold quality
metanephros cortex	UBERON:0010533	96.70	gold quality
coronary artery	UBERON:0001621	96.69	gold quality
mononuclear cell	CL:0000842	96.59	gold quality
cardiac ventricle	UBERON:0002082	96.54	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.03
E-MTAB-6678	yes	4.23
E-HCAD-5	no	2.22

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
RILP	Activation

Upstream regulators (CollecTRI, top): MCM2

miRNA regulators (miRDB)

18 targeting SNF8, 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-4482-3P	99.98	72.50	3147
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-5690	99.25	67.58	1012
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-4464	98.95	67.73	820
HSA-MIR-4748	98.95	67.53	810
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-890	97.47	68.67	982
HSA-MIR-6834-5P	96.25	64.88	823

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 95.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 7)

• mammalian ESCRTII is made up of hVps25p, hVps22p, and hVps36p and may be redundant, cargo-specific, or not required for protein sorting at the multivesicular body (PMID:16371348)
• there are probably multiple pathways for protein sorting/multivesicular body vesicle formation in human cells and that human immunodeficiency virus type 1 does not utilize an ESCRT-II-dependent pathway to leave the cell (PMID:16973552)
• Vps22 has an important role in ligand-induced EGFR and CXCR4 turnover; termination of EGF signaling occurs prior to ESCRT-II engagement (PMID:17714434)
• Modulating SNF8 expression levels alters the TRPC6 channel current and can modulate activation of NFAT-mediated transcription downstream of gain-of-function mutant TRPC6. (PMID:23171048)
• Taken together, these data suggest an active role for ESCRT-II and CHMP6 in ESCRT-mediated abscission (PMID:25232011)
• data describe an unappreciated role for EAP30 in IRF3-dependent innate antiviral response in the nucleus. (PMID:29084253)
• Bi-allelic variants in SNF8 cause a disease spectrum ranging from severe developmental and epileptic encephalopathy to syndromic optic atrophy. (PMID:38423010)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	snf8	ENSDARG00000058076
mus_musculus	Snf8	ENSMUSG00000006058
rattus_norvegicus	Snf8	ENSRNOG00000006500
drosophila_melanogaster	lsn	FBGN0260940
caenorhabditis_elegans		WBGENE00016167

Protein

Protein identifiers

Vacuolar-sorting protein SNF8 — Q96H20 (reviewed: Q96H20)

Alternative names: ELL-associated protein of 30 kDa, ESCRT-II complex subunit VPS22

All UniProt accessions (8): D6RBI1, D6RFY6, D6RJ86, Q96H20, H0Y8S5, I3L2X5, I3L457, K7EPV2

UniProt curated annotations — full annotation on UniProt →

Function. Component of the endosomal sorting complex required for transport II (ESCRT-II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs, and plays a role in autophagy. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation by participating in derepression of transcription by RNA polymerase II, possibly via its interaction with ELL. Required for degradation of both endocytosed EGF and EGFR, but not for the EGFR ligand-mediated internalization. It is also required for the degradation of CXCR4. Required for the exosomal release of SDCBP, CD63 and syndecan.

Subunit / interactions. Component of the endosomal sorting complex required for transport II (ESCRT-II), composed of SNF8, VPS25 and VPS36. SNF8 is essential for the stability of the ESCRT-II complex. ESCRT-II interacts with ELL. Interacts with TSG101 (via the C-terminal domain). Interacts with RILPL1 (via the N-terminal domain); which recruits ESCRT-II to the endosome membranes. Interacts with 14-3-3 proteins.

Subcellular location. Cytoplasm. Endosome membrane. Nucleus. Late endosome membrane.

Disease relevance. Developmental and epileptic encephalopathy 115 (DEE115) [MIM:620783] A form of epileptic encephalopathy, a heterogeneous group of early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE115 is an autosomal recessive, severe form characterized by onset soon after birth. Affected individuals show massive reduction of white matter, hypo- or aplasia of the corpus callosum, and neurodevelopmental arrest. Death in the first year of life may occur. The disease is caused by variants affecting the gene represented in this entry. Neurodevelopmental disorder plus optic atrophy (NEDOA) [MIM:620784] An autosomal recessive disorder characterized by mild developmental delay, intellectual disability and childhood-onset optic atrophy or ataxia. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the SNF8 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96H20-1	1	yes
Q96H20-2	2

RefSeq proteins (4): NP_001304121, NP_001304122, NP_001304123, NP_009172* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016689	ESCRT-2_cplx_Snf8	Family
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR040608	Snf8/Vps36	Family

Pfam: PF04157

UniProt features (30 total): helix 11, strand 7, sequence variant 5, turn 2, chain 1, coiled-coil region 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3CUQ	X-RAY DIFFRACTION	2.61
2ZME	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96H20-F1	85.17	0.49

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 (1): 4

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-917729	Endosomal Sorting Complex Required For Transport (ESCRT)
R-HSA-9610379	HCMV Late Events
R-HSA-1643685	Disease
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-5663205	Infectious disease
R-HSA-9609646	HCMV Infection
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 240 (showing top): REACTOME_ENDOSOMAL_SORTING_COMPLEX_REQUIRED_FOR_TRANSPORT_ESCRT, GOBP_ENDOSOME_ORGANIZATION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_VESICLE_LOCALIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_VESICLE_ORGANIZATION, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_VACUOLAR_TRANSPORT, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (14): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of gene expression (GO:0010628), macroautophagy (GO:0016236), endocytic recycling (GO:0032456), multivesicular body assembly (GO:0036258), regulation of protein catabolic process (GO:0042176), protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043328), early endosome to late endosome transport (GO:0045022), positive regulation of protein catabolic process (GO:0045732), regulation of protein complex stability (GO:0061635), multivesicular body sorting pathway (GO:0071985), membrane fission (GO:0090148), positive regulation of exosomal secretion (GO:1903543), protein transport (GO:0015031)

GO Molecular Function (4): lipid binding (GO:0008289), channel regulator activity (GO:0016247), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (14): ESCRT II complex (GO:0000814), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), endosome membrane (GO:0010008), membrane (GO:0016020), late endosome membrane (GO:0031902), perinuclear region of cytoplasm (GO:0048471), recycling endosome (GO:0055037), extracellular exosome (GO:0070062), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Membrane Trafficking	1
HCMV Infection	1
Vesicle-mediated transport	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	3
protein catabolic process	2
binding	2
endosome membrane	2
endosome	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
autophagosome assembly	1
autophagy	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
multivesicular body organization	1
organelle assembly	1
regulation of catabolic process	1
regulation of protein metabolic process	1
intracellular protein transport	1
late endosome to vacuole transport via multivesicular body sorting pathway	1
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	1
protein localization to vacuole	1
establishment of protein localization to vacuole	1
vesicle-mediated transport between endosomal compartments	1
positive regulation of catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
regulation of biological quality	1
vesicle-mediated transport	1
membrane organization	1
positive regulation of cellular component biogenesis	1
positive regulation of exocytosis	1
regulation of exosomal secretion	1
exosomal secretion	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
channel activity	1
transporter regulator activity	1

Protein interactions and networks

STRING

1034 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNF8	VPS25	Q9BRG1	999
SNF8	VPS36	Q86VN1	999
SNF8	CHMP6	Q96FZ7	970
SNF8	ELL	P55199	931
SNF8	VPS28	Q9UK41	869
SNF8	A0A140T963	A0A140T963	790
SNF8	CHMP3	Q9Y3E7	776
SNF8	CHMP2A	O43633	710
SNF8	TSG101	Q99816	708
SNF8	VPS37C	A5D8V6	696
SNF8	CHMP1A	Q9HD42	689
SNF8	HGS	O14964	667
SNF8	VTA1	Q9NP79	645
SNF8	CHMP4C	Q96CF2	642
SNF8	UBE2Z	Q9H832	623

IntAct

135 interactions, top by confidence:

A	B	Type	Score
SNF8	VPS25	psi-mi:“MI:0915”(physical association)	0.940
VPS25	SNF8	psi-mi:“MI:0915”(physical association)	0.940
VPS36	SNF8	psi-mi:“MI:0915”(physical association)	0.800
VPS36	SNF8	psi-mi:“MI:0914”(association)	0.800
VPS25	VPS36	psi-mi:“MI:0914”(association)	0.800
TRIM54	SNF8	psi-mi:“MI:0915”(physical association)	0.720
SNF8	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
VAC14	SNF8	psi-mi:“MI:0915”(physical association)	0.670
SNF8	VAC14	psi-mi:“MI:0915”(physical association)	0.670
SNF8	MCM2	psi-mi:“MI:0915”(physical association)	0.630
MCM2	SNF8	psi-mi:“MI:0915”(physical association)	0.630
MCM2	SNF8	psi-mi:“MI:0407”(direct interaction)	0.630
SNF8	MCM2	psi-mi:“MI:0407”(direct interaction)	0.630

BioGRID (132): SNF8 (Two-hybrid), VAC14 (Two-hybrid), TRIM54 (Two-hybrid), VPS25 (Two-hybrid), VPS25 (Two-hybrid), SNF8 (Two-hybrid), NIF3L1 (Two-hybrid), SNF8 (Co-fractionation), SNF8 (Co-fractionation), SNF8 (Co-fractionation), SNF8 (Co-fractionation), SNF8 (Co-fractionation), SNF8 (Co-fractionation), TLN2 (Co-fractionation), VPS25 (Two-hybrid)

ESM2 similar proteins: A0JN39, A0MT11, A1Z3X3, A4GWN3, A4QNE0, A5PK00, D2SW95, F1LNJ2, O35841, O60763, O75643, P0C0A2, P23514, P41541, P49754, P53618, Q0JNK5, Q2YDI2, Q53PC7, Q5EAE3, Q5KU39, Q5R922, Q5RJU0, Q5RK19, Q5U3V9, Q5ZIA5, Q5ZKG8, Q640W6, Q66HV4, Q6DDF4, Q6GLK9, Q6NRL4, Q6P4T2, Q7ZVK4, Q80UM3, Q86VN1, Q8BHL5, Q8K2G4, Q8RWF0, Q8WUN7

Diamond homologs: O94663, Q12483, Q54RC4, Q5M759, Q5RJU0, Q5RK19, Q5U3V9, Q96H20, Q9CZ28, Q9LIJ4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SNF8	“form complex”	“ESCRT-II complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
Endosomal Sorting Complex Required For Transport (ESCRT)	5	42.8×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	0
Uncertain significance	28
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
2664478	NM_007241.4(SNF8):c.501C>A (p.Tyr167Ter)	Pathogenic
2664479	NM_007241.4(SNF8):c.572G>A (p.Gly191Asp)	Pathogenic
2664480	NM_007241.4(SNF8):c.236C>T (p.Pro79Leu)	Pathogenic
2664481	NM_007241.4(SNF8):c.623G>T (p.Arg208Leu)	Pathogenic
2664482	NM_007241.4(SNF8):c.423-1G>C	Pathogenic
2664483	NM_007241.4(SNF8):c.673_683delinsTGGA (p.Asp225fs)	Pathogenic

SpliceAI

1428 predictions. Top by Δscore:

Variant	Effect	Δscore
17:48936168:A:AC	donor_gain	1.0000
17:48936169:C:CC	donor_gain	1.0000
17:48936169:CTGA:C	donor_gain	1.0000
17:48936172:A:AC	donor_gain	1.0000
17:48936173:C:CC	donor_gain	1.0000
17:48936179:T:TA	donor_gain	1.0000
17:48936200:C:A	donor_gain	1.0000
17:48937021:T:TA	donor_gain	1.0000
17:48937121:CCAG:C	acceptor_gain	1.0000
17:48937122:CAGC:C	acceptor_gain	1.0000
17:48937123:AGCTA:A	acceptor_loss	1.0000
17:48937125:C:CA	acceptor_loss	1.0000
17:48937125:C:CC	acceptor_gain	1.0000
17:48937126:T:G	acceptor_loss	1.0000
17:48940913:CAA:C	donor_gain	1.0000
17:48940922:A:AC	donor_gain	1.0000
17:48940922:ACAGG:A	donor_gain	1.0000
17:48940923:C:CC	donor_gain	1.0000
17:48940923:CAGG:C	donor_gain	1.0000
17:48940923:CAGGC:C	donor_gain	1.0000
17:48941060:CAT:C	acceptor_gain	1.0000
17:48943920:CTTA:C	donor_loss	1.0000
17:48943921:TTACC:T	donor_loss	1.0000
17:48943922:TACCT:T	donor_loss	1.0000
17:48943923:A:AC	donor_gain	1.0000
17:48943923:ACC:A	donor_loss	1.0000
17:48943924:C:CC	donor_gain	1.0000
17:48943924:C:CT	donor_loss	1.0000
17:48930612:CCTG:C	acceptor_loss	0.9900
17:48930613:C:CC	acceptor_gain	0.9900

AlphaMissense

1677 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:48931670:C:A	W204C	1.000
17:48931670:C:G	W204C	1.000
17:48931672:A:G	W204R	1.000
17:48931672:A:T	W204R	1.000
17:48933266:A:G	L168P	1.000
17:48933317:A:G	L151P	1.000
17:48933329:G:T	A147D	1.000
17:48933330:C:G	A147P	1.000
17:48936221:A:G	L124P	1.000
17:48936242:C:T	G117D	1.000
17:48937022:C:T	G116E	1.000
17:48937045:G:C	C108W	1.000
17:48937047:A:G	C108R	1.000
17:48937064:A:T	V102D	1.000
17:48937068:C:G	G101R	1.000
17:48937070:A:G	L100P	1.000
17:48937081:G:C	F96L	1.000
17:48937081:G:T	F96L	1.000
17:48937083:A:G	F96L	1.000
17:48937108:C:A	W87C	1.000
17:48937108:C:G	W87C	1.000
17:48937110:A:G	W87R	1.000
17:48937110:A:T	W87R	1.000
17:48940929:A:G	L80P	1.000
17:48940929:A:T	L80Q	1.000
17:48940932:G:T	P79Q	1.000
17:48940935:T:A	D78V	1.000
17:48940935:T:C	D78G	1.000
17:48940941:C:A	G76V	1.000
17:48940941:C:T	G76D	1.000

dbSNP variants (sampled 300 via entrez): RS1000139247 (17:48939036 A>G), RS1000756022 (17:48942592 C>G), RS1000824579 (17:48941296 T>C), RS1000938767 (17:48936835 G>A), RS1001019127 (17:48943590 A>T), RS1001170548 (17:48930249 A>G), RS1001572083 (17:48944381 G>C), RS1001621789 (17:48929977 C>A), RS1002300683 (17:48942753 T>C), RS1002759149 (17:48945080 T>A,C), RS1002808619 (17:48944867 T>C,G), RS1002874769 (17:48938932 G>A), RS1002928392 (17:48931024 T>C), RS1003118376 (17:48933466 G>A,C,T), RS1003322129 (17:48940547 T>C)

Disease associations

OMIM: gene MIM:610904 | disease phenotypes: MIM:620783, MIM:620784, MIM:142623

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy 115	Strong	Autosomal recessive
neurodevelopmental disorder plus optic atrophy	Moderate	Autosomal recessive
complex neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (4): developmental and epileptic encephalopathy 115 (MONDO:0968946), neurodevelopmental disorder plus optic atrophy (MONDO:0968947), Hirschsprung disease (MONDO:0018309), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (1): Hirschsprung disease (Orphanet:388)

HPO phenotypes

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

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000405	Conductive hearing impairment
HP:0000609	Optic nerve hypoplasia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001274	Agenesis of corpus callosum
HP:0001302	Pachygyria
HP:0002015	Dysphagia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002283	Global brain atrophy
HP:0002352	Leukoencephalopathy
HP:0002353	EEG abnormality
HP:0002376	Developmental regression
HP:0003577	Congenital onset
HP:0003621	Juvenile onset
HP:0006989	Dysplastic corpus callosum
HP:0008278	Cerebellar cortical atrophy
HP:0011342	Mild global developmental delay
HP:0011463	Childhood onset
HP:0011968	Feeding difficulties
HP:0033454	Tube feeding

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000998_5	Coronary heart disease	2.000000e-08
GCST005414_22	Type 2 diabetes	3.000000e-08
GCST90020028_1420	Hip circumference adjusted for BMI	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	8
Benzo(a)pyrene	increases methylation, decreases expression	2
Lead	affects expression, decreases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
14-deoxy-11,12-didehydroandrographolide	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Cytarabine	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Selenium	increases expression	1
Vitamin E	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT03660176	PHASE3	UNKNOWN	Effects of Butyrate Enemas on Postoperative Intestinal Mobility Disorders in Hirschsprung’s Disease
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT00630838	PHASE2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT00671684	PHASE1/PHASE2	UNKNOWN	Endoscopic Mucosal Resection (EMR) for Diagnosis of Hirschsprung’s Disease
NCT01985646	EARLY_PHASE1	COMPLETED	A Trial on Conservative Treatment for Infants’ Hirschsprung Disease
NCT00478712	Not specified	RECRUITING	Hirschsprung Disease Genetic Study
NCT01515501	Not specified	COMPLETED	Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial (EDGE Trial)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01927809	Not specified	UNKNOWN	Genetic Mosaicism in Hirschsprung’s Disease
NCT02193685	Not specified	UNKNOWN	Identification Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease
NCT02216994	Not specified	UNKNOWN	A New Scoring System Improves Diagnostic Accuracy of Intestinal Dysganglionosis –a Prospective Study
NCT02296008	Not specified	COMPLETED	3D High Resolution Anorectal Manometry in Children After Surgery for Anorectal Disorders
NCT02776176	Not specified	UNKNOWN	Enhanced Recovery After Surgery In Hirschsprung Disease
NCT02857205	Not specified	COMPLETED	MICROPRUNG : Intestinal Microbiota Analysis in Patients With or Without Hirschsprung’s Associated EnteroColitis
NCT03269812	Not specified	UNKNOWN	Laparoscopic Assisted Pull-through Versus Other Surgical Procedures for Treatment of Hirschsprung Disease
NCT03406741	Not specified	COMPLETED	Neuropsychological Development and Functional Outcome Sin Children With Hirschsprung Disease at School Age
NCT03626350	Not specified	ACTIVE_NOT_RECRUITING	Prospective Evaluation of the Efficacy and Safety of Submucosal Endoscopy
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT04020939	Not specified	COMPLETED	The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery.
NCT04106947	Not specified	UNKNOWN	Transition of Care for Patients With Hirschsprung Disease and Anorectal Malformations
NCT04149093	Not specified	UNKNOWN	The Association Between Calretinin and the Function of Ganglion Cells in Hirschsprung Disease
NCT04150120	Not specified	COMPLETED	eHealth as an Aid for Facilitating and Supporting Self-management in Families With Long-term Childhood Illness
NCT04213976	Not specified	UNKNOWN	Ostomy in Continuity or Conventional Ileostomy: a Retrospective Multicentric Analysis
NCT04476225	Not specified	COMPLETED	Induced Pluripotent Stem Cells for Disease Research
NCT04598841	Not specified	COMPLETED	Nutrition Support for Hirschsprung Disease
NCT04622410	Not specified	RECRUITING	Registry for Hirschsprung Disease of the BELAPS
NCT04624334	Not specified	TERMINATED	Non-invasive Assessment of Colonic Motility
NCT04713085	Not specified	COMPLETED	Sacral Neuromodulation in Children and Adolescents
NCT04730128	Not specified	COMPLETED	Translation and Validation of a Disease-specific Questionnaire for Hirschsprung’s Disease in Danish Patients
NCT04837963	Not specified	COMPLETED	Does Hirschsprung Disease Increase the Risk of Febrile Urinary Tract Infection in Children
NCT04957667	Not specified	COMPLETED	Scintigraphic Defecography for Evaluation of Functional Outcome in an Adult Hirschsprung Population
NCT05038345	Not specified	TERMINATED	Hirschsprung Disease Trends in the United States: Analysis of the National Inpatient Sample
NCT05044741	Not specified	COMPLETED	Risk Factors of Perforated HSCR in Neonates
NCT05293353	Not specified	UNKNOWN	Neokare Safety and Tolerability Assessment in Neonates With GI Problems
NCT05307419	Not specified	UNKNOWN	Full Thickness vs. Rectal Suction Biopsy in the Diagnosis of Hirschsprungs Disease
NCT05450991	Not specified	RECRUITING	Long-term Qualitative and Quantitative Outcomes of Children With Hirschsprung’s Disease and Anorectal Malformations