DISP3

Summary

DISP3 (dispatched RND transporter family member 3, HGNC:29251) is a protein-coding gene on chromosome 1p36.22, encoding Protein dispatched homolog 3 (Q9P2K9). Plays a role in neuronal proliferation and differentiation.

Involved in negative regulation of neuron differentiation; positive regulation of lipid metabolic process; and positive regulation of neural precursor cell proliferation. Located in cytoplasm.

Source: NCBI Gene 57540 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 65 total
• MANE Select transcript: NM_020780

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29251
Approved symbol	DISP3
Name	dispatched RND transporter family member 3
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1337
Ensembl gene	ENSG00000204624
Ensembl biotype	protein_coding
OMIM	611251
Entrez	57540

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000294484, ENST00000304391, ENST00000423056, ENST00000922103, ENST00000922104, ENST00000922105

RefSeq mRNA: 1 — MANE Select: NM_020780 NM_020780

CCDS: CCDS41247

Canonical transcript exons

ENST00000294484 — 21 exons

Exon	Start	End
ENSE00001065687	11515369	11515503
ENSE00001065688	11519355	11519503
ENSE00001065696	11519719	11519880
ENSE00001065698	11525176	11525312
ENSE00001065699	11502678	11502897
ENSE00001065701	11514390	11514526
ENSE00001065702	11523942	11524055
ENSE00001065703	11520687	11520848
ENSE00001065705	11516001	11516161
ENSE00001065707	11517463	11517602
ENSE00001506257	11531565	11531710
ENSE00001506258	11530907	11531033
ENSE00001506259	11529787	11529959
ENSE00001506260	11529556	11529686
ENSE00001506261	11526651	11526835
ENSE00001662541	11500990	11502088
ENSE00001706216	11479155	11479372
ENSE00001783669	11536324	11537551
ENSE00003464077	11534381	11534540
ENSE00003637510	11535011	11535124
ENSE00003674493	11535478	11535644

Expression profiles

Bgee: expression breadth broad, 96 present calls, max score 96.19.

FANTOM5 (CAGE): breadth broad, TPM avg 3.2115 / max 211.2762, expressed in 514 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
618	3.1830	508
619	0.0179	8
620	0.0106	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	96.19	gold quality
cortical plate	UBERON:0005343	83.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.38	gold quality
putamen	UBERON:0001874	76.41	gold quality
caudate nucleus	UBERON:0001873	76.39	gold quality
ventricular zone	UBERON:0003053	75.54	gold quality
right frontal lobe	UBERON:0002810	75.07	gold quality
nucleus accumbens	UBERON:0001882	74.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	72.67	gold quality
primary visual cortex	UBERON:0002436	72.00	gold quality
amygdala	UBERON:0001876	71.83	gold quality
right testis	UBERON:0004534	71.82	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	71.47	gold quality
left testis	UBERON:0004533	71.29	gold quality
neocortex	UBERON:0001950	70.83	gold quality
anterior cingulate cortex	UBERON:0009835	70.78	gold quality
forebrain	UBERON:0001890	70.74	gold quality
hypothalamus	UBERON:0001898	70.57	gold quality
frontal cortex	UBERON:0001870	70.44	gold quality
cerebral cortex	UBERON:0000956	70.30	gold quality
prefrontal cortex	UBERON:0000451	70.26	gold quality
Brodmann (1909) area 23	UBERON:0013554	70.07	gold quality
middle temporal gyrus	UBERON:0002771	70.05	gold quality
brain	UBERON:0000955	69.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.59	gold quality
temporal lobe	UBERON:0001871	69.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	69.36	gold quality
testis	UBERON:0000473	68.88	gold quality
occipital lobe	UBERON:0002021	68.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.77

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting DISP3, 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-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-4735-3P	99.14	69.85	777
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-3187-5P	98.36	65.74	1776
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-1285-3P	97.72	67.02	1932

Literature-anchored findings (GeneRIF, showing 3)

• patched domain containing 2 (PTCHD2), yielded a statistically significant P-value of 2.5 x 10(-6) (OR = 0.27) with fewer individuals classified as exhibiting symptoms of dependence to ultraviolet light, a known carcinogen, in the context of tanning (PMID:25041255)
• impact of DISP3 on the proliferation and differentiation of neural precursors (PMID:25281927)
• our findings imply that DISP3 may help dictate the NSC cell fate to either undergo self-renewal or switch to the terminal differentiation cell program. (PMID:28134287)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	disp3	ENSDARG00000036999
mus_musculus	Disp3	ENSMUSG00000041544
rattus_norvegicus	Disp3	ENSRNOG00000026447
drosophila_melanogaster	ptc	FBGN0003892
drosophila_melanogaster	disp	FBGN0029088
drosophila_melanogaster	Ptr	FBGN0262867
caenorhabditis_elegans		WBGENE00004208
caenorhabditis_elegans		WBGENE00004211
caenorhabditis_elegans	ptr-17	WBGENE00004231

Paralogs (10): NPC1L1 (ENSG00000015520), SCAP (ENSG00000114650), PTCH2 (ENSG00000117425), DISP2 (ENSG00000140323), NPC1 (ENSG00000141458), DISP1 (ENSG00000154309), PTCHD1 (ENSG00000165186), PTCHD3 (ENSG00000182077), PTCH1 (ENSG00000185920), PTCHD4 (ENSG00000244694)

Protein

Protein identifiers

Protein dispatched homolog 3 — Q9P2K9 (reviewed: Q9P2K9)

Alternative names: Patched domain-containing protein 2

All UniProt accessions (2): Q9P2K9, Q9UJD7

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in neuronal proliferation and differentiation. Plays a role in the accumulation of cellular cholesterol. Involved in intracellular lipid droplet formation. May contribute to cholesterol homeostasis in neuronal cells.

Subcellular location. Endoplasmic reticulum membrane. Nucleus membrane. Cytoplasmic vesicle membrane.

Tissue specificity. Expressed in brain and testis.

Domain organisation. The SSD (sterol-sensing) domain is necessary for the increase in cellular cholesterol uptake.

Induction. Up-regulated by thyroid hormone T3.

Similarity. Belongs to the patched family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P2K9-1	1	yes
Q9P2K9-2	2

RefSeq proteins (1): NP_065831* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000731	SSD	Domain
IPR004869	MMPL_dom	Domain
IPR042480	DISP3	Family
IPR053954	DUF7023	Domain
IPR053958	HMGCR/SNAP/NPC1-like_SSD	Domain

Pfam: PF03176, PF12349, PF22894

UniProt features (39 total): topological domain 13, transmembrane region 12, sequence variant 6, region of interest 2, glycosylation site 2, chain 1, domain 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2K9-F1	70.84	0.11

Functional residue map

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

Glycosylation sites (2): 163, 1021

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_STEROL_HOMEOSTASIS, GOBP_NEUROGENESIS, GOBP_LIPID_HOMEOSTASIS, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_LIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_SMOOTHENED_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_TRANSPORT, GOBP_LIPID_LOCALIZATION, GOBP_REGULATION_OF_NEURAL_PRECURSOR_CELL_PROLIFERATION

GO Biological Process (10): smoothened signaling pathway (GO:0007224), cholesterol metabolic process (GO:0008203), cell differentiation (GO:0030154), regulation of lipid transport (GO:0032368), cholesterol homeostasis (GO:0042632), negative regulation of neuron differentiation (GO:0045665), positive regulation of lipid metabolic process (GO:0045834), positive regulation of neural precursor cell proliferation (GO:2000179), lipid metabolic process (GO:0006629), steroid metabolic process (GO:0008202)

GO Molecular Function (0):

GO Cellular Component (8): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), nuclear membrane (GO:0031965), nucleus (GO:0005634), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	2
cellular anatomical structure	2
cytoplasm	2
intracellular membrane-bounded organelle	2
organelle membrane	2
cell surface receptor signaling pathway	1
sterol metabolic process	1
secondary alcohol metabolic process	1
cellular developmental process	1
lipid transport	1
regulation of transport	1
regulation of lipid localization	1
sterol homeostasis	1
neuron differentiation	1
negative regulation of cell differentiation	1
regulation of neuron differentiation	1
positive regulation of metabolic process	1
regulation of lipid metabolic process	1
positive regulation of cell population proliferation	1
neural precursor cell proliferation	1
regulation of neural precursor cell proliferation	1
primary metabolic process	1
intracellular anatomical structure	1
endomembrane system	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vesicle membrane	1
cytoplasmic vesicle	1
nucleus	1
nuclear envelope	1
intracellular vesicle	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DISP3	UBIAD1	Q9Y5Z9	951
DISP3	FBXO2	Q9UK22	872
DISP3	PTCHD4	Q6ZW05	601
DISP3	PTCHD1	Q96NR3	553
DISP3	DISP1	Q96F81	458
DISP3	MED22	Q15528	455
DISP3	HECW2	Q9P2P5	444
DISP3	KANSL3	Q9P2N6	423
DISP3	NFU1	Q9UMS0	423
DISP3	GRSF1	Q12849	413
DISP3	UBL4B	Q8N7F7	407
DISP3	ZNF536	O15090	400
DISP3	C9orf78	Q9NZ63	388
DISP3	AAK1	Q2M2I8	384
DISP3	DISP2	A7MBM2	377

IntAct

7 interactions, top by confidence:

A	B	Type	Score
DISP3	RPS14	psi-mi:“MI:0915”(physical association)	0.400
DISP3	DDX21	psi-mi:“MI:0915”(physical association)	0.400
MTNR1B	DISP3	psi-mi:“MI:0915”(physical association)	0.370
MYCBP	DISP3	psi-mi:“MI:0915”(physical association)	0.000
DISP3	RASGRP2	psi-mi:“MI:0915”(physical association)	0.000
DISP3	CA2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): PTCHD2 (Two-hybrid), PTCHD2 (Two-hybrid), PTCHD2 (Two-hybrid), PTCHD2 (Proximity Label-MS), PTCHD2 (Proximity Label-MS), PTCHD2 (Positive Genetic)

ESM2 similar proteins: A0JPH4, A2AGX3, A2RRU4, A3KFU9, A6QM06, A7YWH3, B9U3F2, G5E8P0, O15040, O75129, P97260, Q12770, Q17RG1, Q2M3C6, Q2R2B1, Q32KQ7, Q4R5A4, Q562E2, Q5M9F0, Q5MNU5, Q5RA50, Q5SYB0, Q6GQT6, Q6L8S8, Q6L9W6, Q6PCP7, Q80TL0, Q80Z10, Q80Z30, Q86V42, Q8BHR8, Q8BZB3, Q8C0R7, Q8CIV2, Q8JZL1, Q8K0Z9, Q8K451, Q8NFM7, Q8NFN8, Q8VZJ0

Diamond homologs: A3KFU9, B9U3F2, Q9P2K9, Q9Y6C5, H2L0G5, O35595, O42334, O42335, P18502, Q09614, Q0EEE2, Q13635, Q3KNS1, Q61115, Q90693, Q98864

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	21
Benign	20

Top pathogenic / likely-pathogenic (0)

SpliceAI

4219 predictions. Top by Δscore:

Variant	Effect	Δscore
1:11479369:CGAGG:C	donor_loss	1.0000
1:11479370:GAGGT:G	donor_loss	1.0000
1:11479373:G:GG	donor_gain	1.0000
1:11479373:GT:G	donor_loss	1.0000
1:11479374:T:G	donor_loss	1.0000
1:11502674:GCA:G	acceptor_loss	1.0000
1:11502675:CA:C	acceptor_loss	1.0000
1:11502676:A:AG	acceptor_gain	1.0000
1:11502677:G:GA	acceptor_gain	1.0000
1:11502677:G:GC	acceptor_loss	1.0000
1:11502677:GGCT:G	acceptor_gain	1.0000
1:11502894:CCAG:C	donor_loss	1.0000
1:11502898:G:GG	donor_gain	1.0000
1:11502899:T:G	donor_loss	1.0000
1:11514371:A:AG	acceptor_gain	1.0000
1:11514372:C:G	acceptor_gain	1.0000
1:11514385:CCCAG:C	acceptor_loss	1.0000
1:11514386:CCAGC:C	acceptor_loss	1.0000
1:11514388:A:AG	acceptor_gain	1.0000
1:11514389:G:GA	acceptor_gain	1.0000
1:11514389:GCAAA:G	acceptor_gain	1.0000
1:11514522:CTCAG:C	donor_loss	1.0000
1:11514524:CAGG:C	donor_loss	1.0000
1:11514525:AGGTA:A	donor_loss	1.0000
1:11514526:GGTA:G	donor_loss	1.0000
1:11514527:G:C	donor_loss	1.0000
1:11514528:T:A	donor_loss	1.0000
1:11515501:TTGG:T	donor_loss	1.0000
1:11515502:TGG:T	donor_loss	1.0000
1:11515503:GGT:G	donor_loss	1.0000

AlphaMissense

9005 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:11501935:T:A	C315S	1.000
1:11501935:T:C	C315R	1.000
1:11501936:G:A	C315Y	1.000
1:11501936:G:C	C315S	1.000
1:11501937:C:G	C315W	1.000
1:11501989:T:A	C333S	1.000
1:11501989:T:C	C333R	1.000
1:11501990:G:C	C333S	1.000
1:11502765:T:C	L395P	1.000
1:11514478:A:C	S469R	1.000
1:11514480:C:A	S469R	1.000
1:11514480:C:G	S469R	1.000
1:11515485:T:C	F524L	1.000
1:11515487:C:A	F524L	1.000
1:11515487:C:G	F524L	1.000
1:11516007:A:T	D532V	1.000
1:11520833:T:C	C783R	1.000
1:11520842:T:C	C786R	1.000
1:11520844:T:G	C786W	1.000
1:11501809:T:A	W273R	0.999
1:11501809:T:C	W273R	0.999
1:11501811:G:C	W273C	0.999
1:11501811:G:T	W273C	0.999
1:11501822:T:C	L277P	0.999
1:11501861:T:C	F290S	0.999
1:11501876:T:C	L295P	0.999
1:11501932:T:C	F314L	0.999
1:11501934:C:A	F314L	0.999
1:11501934:C:G	F314L	0.999
1:11501936:G:T	C315F	0.999

dbSNP variants (sampled 300 via entrez): RS1000262866 (1:11508752 C>A,G), RS1000313115 (1:11500921 C>T), RS1000336271 (1:11477613 C>G,T), RS1000491241 (1:11482808 G>A,T), RS1000500704 (1:11484407 T>C), RS1000515791 (1:11502615 T>C), RS1000653206 (1:11502304 G>T), RS1000722183 (1:11517050 T>A,G), RS1000780935 (1:11508486 T>C), RS1000825985 (1:11525137 G>A), RS1000906080 (1:11484099 G>A), RS1000914614 (1:11512257 GT>G,GTT), RS1001034560 (1:11494277 G>C), RS1001088310 (1:11494025 C>T), RS1001129632 (1:11496490 C>T)

Disease associations

OMIM: gene MIM:611251 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010219_2	Attention deficit hyperactivity disorder (inattention symptoms)	6.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression	2
Benzo(a)pyrene	affects methylation	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
licochalcone B	increases expression	1
(+)-JQ1 compound	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Cytarabine	increases expression	1
Endosulfan	increases expression	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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