VPS35L

Summary

VPS35L (VPS35 endosomal protein sorting factor like, HGNC:24641) is a protein-coding gene on chromosome 16p12.3, encoding VPS35 endosomal protein-sorting factor-like (Q7Z3J2). Acts as a component of the retriever complex.

Involved in Golgi to plasma membrane transport and endocytic recycling. Located in endosome. Implicated in Ritscher-Schinzel syndrome.

Source: NCBI Gene 57020 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Ritscher-Schinzel syndrome 3 (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 69 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 87
• MANE Select transcript: NM_020314

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24641
Approved symbol	VPS35L
Name	VPS35 endosomal protein sorting factor like
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC16824
Ensembl gene	ENSG00000103544
Ensembl biotype	protein_coding
OMIM	618981
Entrez	57020

Gene structure

Transcript identifiers

Ensembl transcripts: 44 — 31 protein_coding, 7 retained_intron, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000251143, ENST00000417362, ENST00000513947, ENST00000535164, ENST00000537186, ENST00000538552, ENST00000539322, ENST00000539705, ENST00000540101, ENST00000540240, ENST00000541153, ENST00000542027, ENST00000542263, ENST00000543152, ENST00000543460, ENST00000544275, ENST00000544670, ENST00000546175, ENST00000562446, ENST00000563649, ENST00000566850, ENST00000567245, ENST00000858378, ENST00000858379, ENST00000858380, ENST00000858381, ENST00000858382, ENST00000858383, ENST00000858384, ENST00000858385, ENST00000858386, ENST00000858387, ENST00000925646, ENST00000925647, ENST00000925648, ENST00000925649, ENST00000925650, ENST00000959636, ENST00000959637, ENST00000959638, ENST00000959639, ENST00000959640, ENST00000959641, ENST00000959642

RefSeq mRNA: 5 — MANE Select: NM_020314 NM_001300743, NM_001365293, NM_001365294, NM_001365295, NM_020314

CCDS: CCDS32397

Canonical transcript exons

ENST00000417362 — 31 exons

Exon	Start	End
ENSE00001030975	19573119	19573241
ENSE00001599382	19669160	19669299
ENSE00001614851	19647784	19647882
ENSE00001634343	19644886	19644949
ENSE00001650977	19633092	19633172
ENSE00001653861	19629767	19629820
ENSE00001665698	19640015	19640100
ENSE00001667879	19627694	19627805
ENSE00001669194	19637594	19637656
ENSE00001672058	19699502	19699648
ENSE00001690657	19682225	19682390
ENSE00001730354	19691353	19691471
ENSE00001740172	19628637	19628753
ENSE00001804934	19642396	19642476
ENSE00003460599	19650382	19650459
ENSE00003492236	19601664	19601723
ENSE00003501852	19564851	19564950
ENSE00003516770	19610322	19610415
ENSE00003539476	19591790	19591874
ENSE00003547874	19616114	19616191
ENSE00003580628	19651976	19652090
ENSE00003583820	19581525	19581653
ENSE00003589693	19626177	19626223
ENSE00003593417	19575098	19575122
ENSE00003596287	19616686	19616808
ENSE00003606713	19700378	19701163
ENSE00003618962	19579052	19579128
ENSE00003631395	19608178	19608274
ENSE00003682253	19608974	19609021
ENSE00003686310	19569424	19569591
ENSE00003891409	19555703	19555746

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 92.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.9883 / max 177.2784, expressed in 1768 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153022	16.9004	1752
153021	1.4660	1018
153031	0.4761	208
153032	0.0649	32
153025	0.0409	4
153024	0.0354	23
153023	0.0048	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	92.82	gold quality
stromal cell of endometrium	CL:0002255	92.73	gold quality
colonic epithelium	UBERON:0000397	91.15	gold quality
corpus callosum	UBERON:0002336	91.10	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.92	gold quality
oocyte	CL:0000023	90.60	gold quality
right adrenal gland cortex	UBERON:0035827	90.58	gold quality
right adrenal gland	UBERON:0001233	90.47	gold quality
smooth muscle tissue	UBERON:0001135	90.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.05	gold quality
putamen	UBERON:0001874	90.00	gold quality
left adrenal gland	UBERON:0001234	89.96	gold quality
spinal cord	UBERON:0002240	89.92	gold quality
left adrenal gland cortex	UBERON:0035825	89.87	gold quality
adenohypophysis	UBERON:0002196	89.66	gold quality
right frontal lobe	UBERON:0002810	89.65	gold quality
monocyte	CL:0000576	89.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.61	gold quality
sural nerve	UBERON:0015488	89.60	gold quality
middle temporal gyrus	UBERON:0002771	89.59	gold quality
pituitary gland	UBERON:0000007	89.55	gold quality
mononuclear cell	CL:0000842	89.54	gold quality
adrenal tissue	UBERON:0018303	89.53	gold quality
adrenal cortex	UBERON:0001235	89.51	gold quality
adrenal gland	UBERON:0002369	89.49	gold quality
leukocyte	CL:0000738	89.45	gold quality
caudate nucleus	UBERON:0001873	89.35	gold quality
gall bladder	UBERON:0002110	89.30	gold quality
left testis	UBERON:0004533	89.29	gold quality
amygdala	UBERON:0001876	89.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	38.95
E-HCAD-1	yes	20.45
E-ANND-3	yes	7.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting VPS35L, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-3919	99.87	69.45	2489
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-520A-5P	99.35	66.72	1632
HSA-MIR-525-5P	99.35	66.85	1615
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-548AO-5P	98.55	69.57	1362

Literature-anchored findings (GeneRIF, showing 3)

• Heterotrimer composed of DSCR3, C16orf62 and VPS29 orchestrates endosomal cargo retrieval and recycling. (PMID:28892079)
• Biallelic VPS35L pathogenic variants cause 3C/Ritscher-Schinzel-like syndrome through dysfunction of retriever complex. (PMID:31712251)
• Clinical diversity and molecular mechanism of VPS35L-associated Ritscher-Schinzel syndrome. (PMID:36113987)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vps35l	ENSDARG00000020041
mus_musculus	Vps35l	ENSMUSG00000030982
rattus_norvegicus	Vps35l	ENSRNOG00000016063
drosophila_melanogaster	CG8202	FBGN0037622
caenorhabditis_elegans		WBGENE00017837

Protein

Protein identifiers

VPS35 endosomal protein-sorting factor-like — Q7Z3J2 (reviewed: Q7Z3J2)

Alternative names: Esophageal cancer-associated protein

All UniProt accessions (11): E7EWW0, Q7Z3J2, F5H7K1, F6S1J4, H0YFG6, H3BRV8, H3BTI5, H3BUS7, H3BV68, H3BVG8, I3L1U5

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a component of the retriever complex. The retriever complex is a heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrin alpha-5/beta-1 (ITGA5:ITGB1). The recruitment of the retriever complex to the endosomal membrane involves CCC and WASH complexes. In the endosomes, drives the retrieval and recycling of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo essential for the homeostatic maintenance of numerous cell surface proteins associated with processes that include cell migration, cell adhesion, nutrient supply and cell signaling. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association with the CCC complex and cooperation with the WASH complex on early endosomes. Does not seem to be required for CCC complex stability. (Microbial infection) The heterotrimeric retriever complex, in collaboration with the CCC complex, mediates the exit of human papillomavirus to the cell surface.

Subunit / interactions. Component of the heterotrimeric retriever complex formed by VPS26C, VPS29 and VPS35L. Interacts with VPS29. Interacts with COMMD1, CCDC93 and CCDC22; associates with the CCC (COMMD/CCDC22/CCDC93) complex which contains at least COMMD1 (and possibly other COMM domain-containing proteins), CCDC22 and CCDC93. Interacts with WASHC1, WASHC2A and WASHC2C. Interacts with SNX17 and SNX31.

Subcellular location. Membrane. Endosome.

Disease relevance. Ritscher-Schinzel syndrome 3 (RTSC3) [MIM:619135] A form of Ritscher-Schinzel syndrome, a developmental malformation syndrome characterized by cerebellar brain malformations, congenital heart defects, and craniofacial abnormalities. RTSC3 is an autosomal recessive form. Affected individuals show cranio-cerebello-cardiac anomalies, coloboma, microphthalmia, chondrodysplasia punctata, complicated skeletal malformations, periventricular nodular heterotopia and proteinuria. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the VPS35L family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z3J2-1	1	yes
Q7Z3J2-2	2

RefSeq proteins (5): NP_001287672, NP_001352222, NP_001352223, NP_001352224, NP_064710* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029705	VPS35L	Family

UniProt features (73 total): helix 48, turn 5, strand 5, sequence variant 4, sequence conflict 3, splice variant 3, chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
8ESE	X-RAY DIFFRACTION	1.35
8SYN	ELECTRON MICROSCOPY	2.94
8SYO	ELECTRON MICROSCOPY	2.94
8SYM	ELECTRON MICROSCOPY	3.2
9AU7	ELECTRON MICROSCOPY	3.4
8P0V	ELECTRON MICROSCOPY	6.5
8P0X	ELECTRON MICROSCOPY	7.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z3J2-F1	85.34	0.65

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): 265

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 357 (showing top): MODULE_97, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_182, GOBP_VESICLE_MEDIATED_TRANSPORT, MORF_RAD51L3, GOBP_GOLGI_TO_PLASMA_MEMBRANE_TRANSPORT, GOBP_ENDOCYTIC_RECYCLING, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOCC_SECRETORY_VESICLE, chr16p12, GOCC_SECRETORY_GRANULE_MEMBRANE, GOCC_MEMBRANE_PROTEIN_COMPLEX

GO Biological Process (3): Golgi to plasma membrane transport (GO:0006893), protein transport (GO:0015031), endocytic recycling (GO:0032456)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): endosome (GO:0005768), plasma membrane (GO:0005886), ficolin-1-rich granule membrane (GO:0101003), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
vesicle-mediated transport to the plasma membrane	2
post-Golgi vesicle-mediated transport	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
endosomal transport	1
binding	1
endomembrane system	1
cytoplasmic vesicle	1
membrane	1
cell periphery	1
secretory granule membrane	1
tertiary granule	1
ficolin-1-rich granule	1
cellular anatomical structure	1

Protein interactions and networks

STRING

486 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPS35L	VPS26C	O14972	996
VPS35L	VPS29	Q9UBQ0	994
VPS35L	CCDC93	Q567U6	981
VPS35L	CCDC22	O60826	978
VPS35L	COMMD1	Q8N668	929
VPS35L	SNX17	Q15036	798
VPS35L	SNX27	Q96L92	751
VPS35L	COMMD6	Q7Z4G1	713
VPS35L	VPS26A	O75436	687
VPS35L	COMMD9	Q9P000	687
VPS35L	WASHC2A	Q641Q2	683
VPS35L	DENND10	Q8TCE6	626
VPS35L	VPS35	Q96QK1	593
VPS35L	SNX31	Q8N9S9	539
VPS35L	WASHC1	A8K0Z3	513

IntAct

114 interactions, top by confidence:

A	B	Type	Score
COMMD1	CCDC22	psi-mi:“MI:0914”(association)	0.970
CCDC93	CCDC22	psi-mi:“MI:0914”(association)	0.960
CCDC22	CCDC93	psi-mi:“MI:0914”(association)	0.960
COMMD2	CCDC22	psi-mi:“MI:0914”(association)	0.930
VPS35L	CCDC22	psi-mi:“MI:0914”(association)	0.900
CCDC22	VPS35L	psi-mi:“MI:0914”(association)	0.900
VPS29	VPS35L	psi-mi:“MI:0915”(physical association)	0.840
VPS29	VPS35L	psi-mi:“MI:0407”(direct interaction)	0.840
COMMD1	VPS35L	psi-mi:“MI:0403”(colocalization)	0.810
VPS29	CCDC22	psi-mi:“MI:0914”(association)	0.790
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.790
VPS26C	CCDC22	psi-mi:“MI:0914”(association)	0.790
CCDC93	VPS35L	psi-mi:“MI:0403”(colocalization)	0.780
VPS35L	CCDC93	psi-mi:“MI:0914”(association)	0.780
DENND10	CCDC93	psi-mi:“MI:0914”(association)	0.770
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760

BioGRID (85): C16orf62 (Affinity Capture-Western), C16orf62 (Affinity Capture-Western), CCDC22 (Affinity Capture-Western), CCDC93 (Affinity Capture-Western), C16orf62 (Affinity Capture-Western), C16orf62 (Affinity Capture-MS), C16orf62 (Affinity Capture-MS), C16orf62 (Affinity Capture-MS), C16orf62 (Co-fractionation), TRIM25 (Co-fractionation), C16orf62 (Affinity Capture-MS), C16orf62 (Affinity Capture-MS), C16orf62 (Affinity Capture-MS), C16orf62 (Affinity Capture-MS), C16orf62 (Affinity Capture-MS)

ESM2 similar proteins: A0JNN3, A2AWA9, B1H2N3, B5DEN9, B5DGH9, O43242, O60941, O76031, P14685, P60228, P60229, Q05AY2, Q06364, Q07866, Q0IIL1, Q13330, Q1LUA8, Q28FE2, Q2KJ46, Q3B8M3, Q3T102, Q4QR03, Q4R6G8, Q503N9, Q5F428, Q5R7N3, Q5R8K9, Q5R8N4, Q5RAN1, Q5U2U0, Q5ZLA5, Q62599, Q641X8, Q6DH26, Q6DRI1, Q6GQA1, Q6P6Q9, Q6P7L9, Q7Z3J2, Q8K4B0

Diamond homologs: A4VCH4, Q557H3, Q5R8N4, Q5XI83, Q7Z3J2, Q8BWQ6, Q9VHM2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 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
Neddylation	11	15.3×	9e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	21
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
3068428	NM_020314.7(VPS35L):c.1383+2T>A	Pathogenic
3068429	NM_020314.7(VPS35L):c.2360C>T (p.Pro787Leu)	Pathogenic
989441	NM_020314.7(VPS35L):c.2488G>A (p.Ala830Thr)	Pathogenic
989442	NM_020314.7(VPS35L):c.830dup (p.Cys277fs)	Pathogenic
3777736	NM_020314.7(VPS35L):c.2017del (p.Gln673fs)	Likely pathogenic
4685472	NM_020314.7(VPS35L):c.881T>C (p.Phe294Ser)	Likely pathogenic

SpliceAI

4909 predictions. Top by Δscore:

Variant	Effect	Δscore
16:19564951:G:GG	donor_gain	1.0000
16:19569592:G:GA	donor_loss	1.0000
16:19569593:T:G	donor_loss	1.0000
16:19573115:TTA:T	acceptor_loss	1.0000
16:19573117:A:AG	acceptor_gain	1.0000
16:19573117:AG:A	acceptor_gain	1.0000
16:19573118:G:GA	acceptor_loss	1.0000
16:19573118:G:GG	acceptor_gain	1.0000
16:19573118:GG:G	acceptor_gain	1.0000
16:19573118:GGAC:G	acceptor_gain	1.0000
16:19573118:GGACA:G	acceptor_gain	1.0000
16:19573240:TT:T	donor_gain	1.0000
16:19573240:TTGT:T	donor_loss	1.0000
16:19573241:TGTG:T	donor_loss	1.0000
16:19573242:G:GG	donor_gain	1.0000
16:19573243:TGAG:T	donor_loss	1.0000
16:19573244:G:GA	donor_loss	1.0000
16:19579046:GTTTA:G	acceptor_loss	1.0000
16:19579049:TAG:T	acceptor_loss	1.0000
16:19579050:A:AG	acceptor_gain	1.0000
16:19579050:AGGC:A	acceptor_loss	1.0000
16:19579051:G:GG	acceptor_gain	1.0000
16:19579125:GGAG:G	donor_gain	1.0000
16:19579126:G:GT	donor_gain	1.0000
16:19579126:GAG:G	donor_gain	1.0000
16:19579127:AGGT:A	donor_loss	1.0000
16:19579128:GGTG:G	donor_loss	1.0000
16:19579130:T:G	donor_loss	1.0000
16:19581522:CA:C	acceptor_loss	1.0000
16:19581523:A:AC	acceptor_loss	1.0000

AlphaMissense

6388 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:19581598:T:C	L195P	1.000
16:19581609:T:A	W199R	1.000
16:19581609:T:C	W199R	1.000
16:19581611:G:C	W199C	1.000
16:19581611:G:T	W199C	1.000
16:19581637:T:C	L208P	1.000
16:19601682:G:C	R248P	1.000
16:19608228:A:G	N279D	1.000
16:19608230:T:A	N279K	1.000
16:19608230:T:G	N279K	1.000
16:19608231:T:A	W280R	1.000
16:19608231:T:C	W280R	1.000
16:19608233:G:C	W280C	1.000
16:19608233:G:T	W280C	1.000
16:19608240:A:C	K283Q	1.000
16:19608240:A:G	K283E	1.000
16:19608241:A:T	K283M	1.000
16:19608242:G:C	K283N	1.000
16:19608242:G:T	K283N	1.000
16:19608256:G:T	R288M	1.000
16:19629791:T:A	W509R	1.000
16:19629791:T:C	W509R	1.000
16:19573182:T:A	W117R	0.999
16:19573182:T:C	W117R	0.999
16:19581586:T:C	L191P	0.999
16:19581606:G:C	A198P	0.999
16:19581610:G:C	W199S	0.999
16:19581625:A:T	K204I	0.999
16:19581626:A:C	K204N	0.999
16:19581626:A:T	K204N	0.999

dbSNP variants (sampled 300 via entrez): RS1000011122 (16:19659053 G>C,T), RS1000013531 (16:19677351 G>A), RS1000055861 (16:19662252 C>A,T), RS1000068965 (16:19634744 T>C), RS1000087345 (16:19570924 C>A,T), RS1000107699 (16:19624530 A>T), RS1000134520 (16:19615553 G>A,C), RS1000141151 (16:19571181 A>G), RS1000162674 (16:19641231 A>T), RS1000175610 (16:19627124 A>G,T), RS1000207118 (16:19671947 G>T), RS1000236703 (16:19600774 A>C), RS1000265615 (16:19583190 C>T), RS1000271085 (16:19700082 G>C), RS1000289993 (16:19607087 T>A)

Disease associations

OMIM: gene MIM:618981 | disease phenotypes: MIM:220210, MIM:619135

GenCC curated gene-disease

Disease	Classification	Inheritance
Ritscher-Schinzel syndrome 3	Limited	Autosomal recessive
Ritscher-Schinzel syndrome	Limited	Autosomal recessive

Mondo (2): Ritscher-Schinzel syndrome (MONDO:0019078), Ritscher-Schinzel syndrome 3 (MONDO:0030864)

Orphanet (1): 3C syndrome (Orphanet:7)

HPO phenotypes

87 total (30 of 87 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000202	Orofacial cleft
HP:0000219	Thin upper lip vermilion
HP:0000235	Abnormal cranial suture/fontanelle morphology
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000260	Wide anterior fontanel
HP:0000269	Prominent occiput
HP:0000316	Hypertelorism
HP:0000329	Facial hemangioma
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000384	Preauricular skin tag
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000501	Glaucoma
HP:0000567	Chorioretinal coloboma
HP:0000568	Microphthalmia
HP:0000612	Iris coloboma
HP:0000648	Optic atrophy
HP:0000835	Adrenal hypoplasia
HP:0000921	Missing ribs
HP:0001156	Brachydactyly

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004797_8	Brain volume in infants (grey matter)	8.000000e-07
GCST005051_26	Obstructive sleep apnea trait (apnea hypopnea index)	9.000000e-06
GCST005051_27	Obstructive sleep apnea trait (apnea hypopnea index)	3.000000e-07
GCST006528_3	Barrett’s esophagus x pack-years of smoking exposure interaction	8.000000e-07
GCST008154_55	Trunk fat mass	4.000000e-06
GCST008157_71	Body fat mass	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008368	infant grey matter volume measurement
EFO:0007817	sleep apnea measurement
EFO:0006526	pack-years measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535313	3C syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	4
bisphenol A	decreases expression, decreases methylation, increases expression	3
sodium arsenite	decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression	2
Acetaminophen	decreases expression	2
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
butyraldehyde	decreases expression	1
aflatoxin B2	increases methylation	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Dronabinol	increases expression	1
Theophylline	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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