PTCHD4

Summary

PTCHD4 (patched domain containing 4, HGNC:21345) is a protein-coding gene on chromosome 6p12.3, encoding Patched domain-containing protein 4 (Q6ZW05). Could act as a repressor of canonical hedgehog signaling by antagonizing the effects of SMO, as suggested by down-regulation of hedgehog target genes, including GLI1, PTCH1, and PTCH2 in PTCHD4-expressing cells.

Predicted to be active in membrane.

Source: NCBI Gene 442213 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 139 total
• MANE Select transcript: NM_001384253

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21345
Approved symbol	PTCHD4
Name	patched domain containing 4
Location	6p12.3
Locus type	gene with protein product
Status	Approved
Aliases	PTCH53, SLC65C2, FLJ41841, dJ402H5.2
Ensembl gene	ENSG00000244694
Ensembl biotype	protein_coding
OMIM	616908
Entrez	442213

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000339488, ENST00000398738, ENST00000679966

RefSeq mRNA: 4 — MANE Select: NM_001384253 NM_001013732, NM_001384253, NM_001410910, NM_207499

CCDS: CCDS93929, CCDS93930

Canonical transcript exons

ENST00000339488 — 5 exons

Exon	Start	End
ENSE00001534635	48068230	48068641
ENSE00001806261	47856673	47879936
ENSE00002043305	48008634	48009114
ENSE00003910363	48111049	48111197
ENSE00003915043	48068953	48069926

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 70.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1021 / max 478.2267, expressed in 1104 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73904	8.6212	1048
73899	0.1199	57
73900	0.0955	52
73905	0.0951	29
73898	0.0635	36
73901	0.0553	26
73902	0.0516	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	70.52	gold quality
islet of Langerhans	UBERON:0000006	63.13	gold quality
calcaneal tendon	UBERON:0003701	61.80	gold quality
apex of heart	UBERON:0002098	61.45	gold quality
ascending aorta	UBERON:0001496	59.06	gold quality
thoracic aorta	UBERON:0001515	59.05	gold quality
buccal mucosa cell	CL:0002336	58.32	gold quality
smooth muscle tissue	UBERON:0001135	57.47	gold quality
adenohypophysis	UBERON:0002196	57.43	gold quality
descending thoracic aorta	UBERON:0002345	57.39	gold quality
endocervix	UBERON:0000458	57.00	gold quality
prefrontal cortex	UBERON:0000451	56.30	gold quality
aorta	UBERON:0000947	55.99	gold quality
ventricular zone	UBERON:0003053	55.88	gold quality
left lobe of thyroid gland	UBERON:0001120	55.09	gold quality
right lung	UBERON:0002167	54.45	gold quality
colonic epithelium	UBERON:0000397	54.31	gold quality
tendon	UBERON:0000043	54.19	gold quality
thyroid gland	UBERON:0002046	54.19	gold quality
pituitary gland	UBERON:0000007	53.87	gold quality
popliteal artery	UBERON:0002250	53.86	gold quality
tibial artery	UBERON:0007610	53.81	gold quality
gall bladder	UBERON:0002110	53.78	gold quality
left coronary artery	UBERON:0001626	53.48	gold quality
coronary artery	UBERON:0001621	52.57	gold quality
tibial nerve	UBERON:0001323	52.46	gold quality
skin of hip	UBERON:0001554	51.98	silver quality
omental fat pad	UBERON:0010414	51.77	gold quality
peritoneum	UBERON:0002358	51.74	gold quality
medial globus pallidus	UBERON:0002477	51.74	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	938.51
E-HCAD-35	yes	68.31
E-ANND-3	no	5.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting PTCHD4, 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-6077	99.99	68.04	2299
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4289	98.26	66.90	810
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-4330	95.44	66.39	993
HSA-MIR-1238-3P	95.27	62.25	552
HSA-MIR-877-5P	94.62	66.30	710

Literature-anchored findings (GeneRIF, showing 1)

• Data indicate that tumor suppressor p53 can suppress canonical Hedgehog signaling via induction of patched domain containing 4 (PTCH53), a PTCH1 homolog. (PMID:25296753)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptchd4	ENSDARG00000008249
mus_musculus	Ptchd4	ENSMUSG00000042256
rattus_norvegicus	Ptchd4	ENSRNOG00000012708
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), DISP3 (ENSG00000204624)

Protein

Protein identifiers

Patched domain-containing protein 4 — Q6ZW05 (reviewed: Q6ZW05)

Alternative names: p53-regulated patched protein

All UniProt accessions (3): A0A7P0TAD5, H0Y3Q6, Q6ZW05

UniProt curated annotations — full annotation on UniProt →

Function. Could act as a repressor of canonical hedgehog signaling by antagonizing the effects of SMO, as suggested by down-regulation of hedgehog target genes, including GLI1, PTCH1, and PTCH2 in PTCHD4-expressing cells.

Subcellular location. Membrane.

Induction. Induced by TP53.

Similarity. Belongs to the patched family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6ZW05-1	1	yes
Q6ZW05-2	2
Q6ZW05-3	3
Q6ZW05-4	4

RefSeq proteins (4): NP_001013754, NP_001371182, NP_001397839, NP_997382 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000731	SSD	Domain
IPR003392	PTHD_SSD	Domain
IPR051697	Patched_domain-protein	Family

Pfam: PF02460

UniProt features (21 total): transmembrane region 12, splice variant 5, chain 1, domain 1, glycosylation site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZW05-F1	82.18	0.34

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 (1): 762

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): AHRARNT_01, FOXO4_01, FOXO1_01, AAAYRNCTG_UNKNOWN, EVI1_05, chr6p12, BRN2_01, OCT1_03, HNF4_DR1_Q3, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, EVI1_01, CCCNNNNNNAAGWT_UNKNOWN, IRF_Q6, GATA1_03, MYB_Q3

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

370 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTCHD4	DISP3	Q9P2K9	601
PTCHD4	TMEM178A	Q8NBL3	475
PTCHD4	HIVEP1	P15822	457
PTCHD4	TSTD2	Q5T7W7	399
PTCHD4	ZNF726	A6NNF4	391
PTCHD4	SAMD10	Q9BYL1	370
PTCHD4	CHRDL2	Q6WN34	367
PTCHD4	SPATA18	Q8TC71	364
PTCHD4	TMEM200C	A6NKL6	351
PTCHD4	ZMAT3	Q9HA38	336
PTCHD4	ZNF544	Q6NX49	330
PTCHD4	NHSL2	Q5HYW2	322
PTCHD4	PANK1	Q8TE04	318
PTCHD4	EDA2R	Q9HAV5	308
PTCHD4	ENC1	O14682	306

IntAct

0 interactions, top by confidence:

BioGRID (1): PTCHD4 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2AIR5, A5PK40, A6NFX1, B9EKX1, D2HKB0, D3ZG27, F1NCD6, O60242, P23979, P46098, P62955, P62956, P62957, Q08DW9, Q0VBU9, Q13635, Q14B62, Q3T9X0, Q4R766, Q504N2, Q5H8A4, Q5RB09, Q5RIV7, Q5T4D3, Q5VTY9, Q5VYX0, Q5VZY2, Q5ZIN0, Q61115, Q66H95, Q6AYT7, Q6ZW05, Q80ZF8, Q8BG19, Q8BWB6, Q8IZD6, Q8N2K0, Q8N6M3, Q8NEB5, Q8NHX9

Diamond homologs: B9EKX1, Q14B62, Q5RIV7, Q6ZW05, Q96NR3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	128
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1742 predictions. Top by Δscore:

Variant	Effect	Δscore
6:47879936:CCT:C	acceptor_loss	1.0000
6:48008677:T:A	donor_gain	1.0000
6:48009114:CCT:C	acceptor_gain	1.0000
6:48068212:ATAGC:A	donor_gain	1.0000
6:47879933:TGAC:T	acceptor_gain	0.9900
6:47879936:CCTAA:C	acceptor_gain	0.9900
6:47879937:C:CC	acceptor_gain	0.9900
6:47879940:A:AC	acceptor_gain	0.9900
6:47879940:A:C	acceptor_gain	0.9900
6:47879943:T:C	acceptor_gain	0.9900
6:47879943:T:TC	acceptor_gain	0.9900
6:47879944:T:C	acceptor_gain	0.9900
6:47989838:C:CT	donor_gain	0.9900
6:47990831:T:C	acceptor_gain	0.9900
6:47998679:C:CT	donor_gain	0.9900
6:47998680:T:TT	donor_gain	0.9900
6:47998713:A:AC	donor_gain	0.9900
6:47998714:C:CC	donor_gain	0.9900
6:47998714:CTT:C	donor_gain	0.9900
6:48009110:CCATC:C	acceptor_gain	0.9900
6:48009111:CATC:C	acceptor_gain	0.9900
6:48009111:CATCC:C	acceptor_gain	0.9900
6:48009116:T:C	acceptor_gain	0.9900
6:48009116:T:TC	acceptor_gain	0.9900
6:48009124:A:T	acceptor_gain	0.9900
6:47879942:G:GC	acceptor_gain	0.9800
6:47879944:T:TC	acceptor_gain	0.9800
6:47879945:T:C	acceptor_gain	0.9800
6:47879945:T:TC	acceptor_gain	0.9800
6:48009112:ATC:A	acceptor_gain	0.9800

AlphaMissense

5608 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:47879024:C:G	R607P	1.000
6:47879196:A:G	W550R	1.000
6:47879196:A:T	W550R	1.000
6:47879028:A:G	S606P	0.999
6:47879194:C:A	W550C	0.999
6:47879194:C:G	W550C	0.999
6:48008961:A:G	W194R	0.999
6:48008961:A:T	W194R	0.999
6:47879031:C:G	A605P	0.998
6:47879120:A:G	L575P	0.998
6:47879444:A:T	V467D	0.998
6:47879452:C:A	K464N	0.998
6:47879452:C:G	K464N	0.998
6:47879860:C:A	R328S	0.998
6:47879860:C:G	R328S	0.998
6:47879898:A:G	W316R	0.998
6:47879898:A:T	W316R	0.998
6:48008821:G:C	S240R	0.998
6:48008821:G:T	S240R	0.998
6:48008823:T:G	S240R	0.998
6:48008959:C:A	W194C	0.998
6:48008959:C:G	W194C	0.998
6:48009032:G:T	A170D	0.998
6:47878433:G:C	P804R	0.997
6:47878636:A:C	F736L	0.997
6:47878636:A:T	F736L	0.997
6:47878638:A:G	F736L	0.997
6:47878742:C:T	G701D	0.997
6:47878743:C:G	G701R	0.997
6:47878752:C:G	G698R	0.997

dbSNP variants (sampled 300 via entrez): RS1000013743 (6:47927221 TAAA>T), RS1000021414 (6:48038682 G>A,T), RS1000022864 (6:48056989 G>T), RS1000039318 (6:47901098 G>A,T), RS1000044960 (6:48018332 T>C), RS1000078178 (6:47928154 C>T), RS1000078521 (6:48050436 A>G), RS1000084113 (6:48045043 T>C), RS1000109064 (6:47932495 T>G), RS1000116372 (6:47906361 T>C), RS1000138437 (6:48012621 G>A), RS1000145960 (6:47895659 G>A,T), RS1000149978 (6:47856211 T>C), RS1000156626 (6:47953140 C>A,T), RS1000163265 (6:48004571 G>C)

Disease associations

OMIM: gene MIM:616908 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002449_5	Plasma omega-6 polyunsaturated fatty acid levels (arachidonic acid)	3.000000e-06
GCST008810_50	Smoking initiation (ever regular vs never regular)	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0005670	smoking initiation

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
bisphenol A	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
sodium arsenite	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Allergens	increases expression	1
Arsenic	increases methylation	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Lucanthone	increases expression	1
Methotrexate	increases expression	1
Progesterone	decreases expression	1
Quercetin	increases expression	1
Thimerosal	increases expression	1
Thiram	decreases expression	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
Oxyquinoline	increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Cyclosporine	decreases expression	1
Sodium Selenite	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TH44	HAP1 PTCHD4 (-) 1	Cancer cell line	Male
CVCL_TH45	HAP1 PTCHD4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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