PTCHD3

Summary

PTCHD3 (patched domain containing 3 (gene/pseudogene), HGNC:24776) is a protein-coding gene on chromosome 10p12.1, encoding Patched domain-containing protein 3 (Q3KNS1). May play a role in sperm development or sperm function.

Located in endoplasmic reticulum and sperm midpiece.

Source: NCBI Gene 374308 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 122 total

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24776
Approved symbol	PTCHD3
Name	patched domain containing 3 (gene/pseudogene)
Location	10p12.1
Locus type	gene with protein product
Status	Approved
Aliases	PTR, SLC65C3, FLJ44037
Ensembl gene	ENSG00000182077
Ensembl biotype	protein_coding
OMIM	611791
Entrez	374308

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding_LoF

ENST00000642324

RefSeq mRNA: 1 — MANE Select: None NM_001034842

Canonical transcript exons

ENST00000642324 — 4 exons

Exon	Start	End
ENSE00001290367	27413162	27414368
ENSE00001291674	27403212	27403357
ENSE00001329800	27411808	27411929
ENSE00003823222	27397121	27399240

Expression profiles

Bgee: expression breadth broad, 28 present calls, max score 79.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0084 / max 5.0465, expressed in 3 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108764	0.0044	3
108765	0.0039	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.74	gold quality
body of pancreas	UBERON:0001150	54.63	gold quality
pancreas	UBERON:0001264	54.19	gold quality
islet of Langerhans	UBERON:0000006	53.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	52.77	gold quality
testis	UBERON:0000473	52.56	gold quality
right testis	UBERON:0004534	50.25	gold quality
left testis	UBERON:0004533	49.79	gold quality
thoracic mammary gland	UBERON:0005200	47.08	gold quality
omental fat pad	UBERON:0010414	46.98	gold quality
lymph node	UBERON:0000029	46.77	silver quality
adipose tissue	UBERON:0001013	45.33	gold quality
subcutaneous adipose tissue	UBERON:0002190	43.40	gold quality
colonic epithelium	UBERON:0000397	41.17	gold quality
placenta	UBERON:0001987	40.94	silver quality
vermiform appendix	UBERON:0001154	40.64	gold quality
cortical plate	UBERON:0005343	39.79	gold quality
ganglionic eminence	UBERON:0004023	38.78	gold quality
muscle tissue	UBERON:0002385	38.32	gold quality
skeletal muscle tissue	UBERON:0001134	37.82	gold quality
lower esophagus mucosa	UBERON:0035834	37.74	gold quality
granulocyte	CL:0000094	37.47	gold quality
fallopian tube	UBERON:0003889	37.05	silver quality
duodenum	UBERON:0002114	36.64	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
apex of heart	UBERON:0002098	36.25	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
smooth muscle tissue	UBERON:0001135	36.07	gold quality
gall bladder	UBERON:0002110	35.91	gold quality
mucosa of stomach	UBERON:0001199	35.65	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting PTCHD3, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-6824-5P	97.41	68.43	583
HSA-MIR-514A-3P	96.43	67.77	1048
HSA-MIR-514B-3P	96.43	67.77	1048
HSA-MIR-4278	95.28	65.49	351
HSA-MIR-6789-5P	94.05	66.19	285

Literature-anchored findings (GeneRIF, showing 2)

• Results indicate that Ptchd3 is a novel male germ cell-specific gene and may be involved in the Hh signaling to regulate sperm development and/or sperm function. (PMID:17904097)
• PTCHD3 nulls: rare copy number and sequence variants suggest a non-essential gene. (PMID:21439084)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptchd3a	ENSDARG00000010075
danio_rerio	ptchd3l	ENSDARG00000068874
mus_musculus	Ptchd3	ENSMUSG00000039198
rattus_norvegicus	Ptchd3	ENSRNOG00000046946
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), PTCH1 (ENSG00000185920), DISP3 (ENSG00000204624), PTCHD4 (ENSG00000244694)

Protein

Protein identifiers

Patched domain-containing protein 3 — Q3KNS1 (reviewed: Q3KNS1)

Alternative names: Patched-related protein

All UniProt accessions (0):

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in sperm development or sperm function. However, does not appear to have an essential role in spermatogenesis or male fertility.

Subcellular location. Cell projection. Cilium. Flagellum membrane. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in germ cells of the testis (at protein level). Detected in blood lymph, colon, small intestine, ovary, testis, prostate, thymus and spleen with highest levels in testis.

Polymorphism. A stop codon in the gene coding for this protein at position Glu-768 is responsible for functional diversity thus producing a pseudogene. The copy number of PTCHD3 varies between individuals with some individuals having no copy of the gene due to a 102,624 base pair deletion spanning the PTCHD3 gene. This deletion does not appear to be associated with an overt phenotype and is found in 0.6-1.6% of individuals of European ancestry.

Similarity. Belongs to the patched family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q3KNS1-1	1	yes
Q3KNS1-2	2

RefSeq proteins (1): NP_001030014 (*=MANE)

Domains & families (InterPro)

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

Pfam: PF02460

UniProt features (36 total): transmembrane region 13, sequence variant 8, glycosylation site 6, compositionally biased region 3, splice variant 2, chain 1, domain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3KNS1-F1	81.80	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.

Glycosylation sites (6): 192, 275, 279, 678, 692, 737

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 20 (showing top): chr10p12, GOCC_MOTILE_CILIUM, GOCC_SPERM_MIDPIECE, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_CILIUM, GOCC_ORGANELLE_SUBCOMPARTMENT, GOCC_9PLUS2_MOTILE_CILIUM, MIR4789_5P, MIR103A_3P_MIR107, MIR6740_3P, MIR6783_5P, MIR6824_5P, MIR4278, MIR6789_5P, DESCARTES_FETAL_PANCREAS_ACINAR_CELLS

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), sperm midpiece (GO:0097225)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
sperm flagellum	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CCDC57	PTCHD3	psi-mi:“MI:0915”(physical association)	0.560
PTCHD3	CLTC	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350
PTCHD3	ABCD4	psi-mi:“MI:0914”(association)	0.350
PTCHD3	CCDC57	psi-mi:“MI:0915”(physical association)	0.000
PTCHD3	thrB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (32): PTCHD3 (Two-hybrid), PTCHD3 (Proximity Label-MS), PTCHD3 (Affinity Capture-MS), PTCHD3 (Negative Genetic), PTCHD3 (Affinity Capture-MS), FAM63A (Affinity Capture-MS), HMGCR (Affinity Capture-MS), SARAF (Affinity Capture-MS), SLC12A6 (Affinity Capture-MS), PPP1R15B (Affinity Capture-MS), ABCD4 (Affinity Capture-MS), TAP2 (Affinity Capture-MS), ST7L (Affinity Capture-MS), PIGO (Affinity Capture-MS), DNAJC18 (Affinity Capture-MS)

ESM2 similar proteins: A4IH46, A8I1B9, A8WGF7, B7ZSK1, D4A7H1, F7B113, M0R3Q7, O02721, P02716, P04759, P16235, P16582, P22888, P25110, P26434, P30730, P35436, P40879, Q00959, Q07001, Q0EEE2, Q12879, Q14B62, Q28005, Q28585, Q2M3M2, Q3KNS1, Q3ZC26, Q4KL91, Q4V8B1, Q5IS45, Q5U3U7, Q5XGK0, Q63424, Q6T3U3, Q6T3U4, Q6YBV0, Q811P0, Q8BLV3, Q8BZ00

Diamond homologs: M0R3Q7, Q0EEE2, Q3KNS1, O35595, Q9UHC9, O15118, O35604, P56941, Q09614, Q8I266, A0A125YWU9, A6NIU2, Q6T3U3, Q6T3U4, Q9VRC9, A3KFU9, B9U3F2, H2L0G5, O42334, O42335, P18502, Q13635, Q61115, Q90693, Q98864, Q9P2K9, Q9Y6C5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	13
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

500 predictions. Top by Δscore:

Variant	Effect	Δscore
10:27399238:CAC:C	acceptor_gain	1.0000
10:27403207:CTCA:C	donor_loss	1.0000
10:27403208:TCA:T	donor_loss	1.0000
10:27403209:CACCT:C	donor_loss	1.0000
10:27403211:C:CT	donor_loss	1.0000
10:27399236:AACAC:A	acceptor_gain	0.9900
10:27399237:ACACC:A	acceptor_loss	0.9900
10:27399238:CACCT:C	acceptor_loss	0.9900
10:27399239:ACCT:A	acceptor_loss	0.9900
10:27399240:CCTG:C	acceptor_loss	0.9900
10:27399241:C:CC	acceptor_gain	0.9900
10:27399241:C:G	acceptor_loss	0.9900
10:27399242:T:C	acceptor_loss	0.9900
10:27403206:ACTC:A	donor_loss	0.9900
10:27403210:A:AC	donor_gain	0.9900
10:27403211:C:CC	donor_gain	0.9900
10:27403211:CCT:C	donor_gain	0.9900
10:27403211:CCTAG:C	donor_gain	0.9900
10:27413252:AGGGT:A	donor_gain	0.9900
10:27399237:ACAC:A	acceptor_gain	0.9800
10:27399238:CACC:C	acceptor_gain	0.9800
10:27399239:AC:A	acceptor_gain	0.9800
10:27399240:CC:C	acceptor_gain	0.9800
10:27403211:CCTA:C	donor_gain	0.9800
10:27403357:CCT:C	acceptor_loss	0.9800
10:27403358:CTGT:C	acceptor_loss	0.9800
10:27403359:T:A	acceptor_loss	0.9800
10:27403366:T:C	acceptor_gain	0.9800
10:27413192:A:AC	donor_gain	0.9800
10:27403210:AC:A	donor_gain	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008712 (10:27413995 G>A), RS1000300846 (10:27406847 G>A,T), RS1000757978 (10:27412361 G>A,T), RS1001107343 (10:27401692 A>G,T), RS1001183489 (10:27416206 T>C,G), RS1001303787 (10:27406318 C>T), RS1001649695 (10:27412536 T>A), RS1001816365 (10:27410777 AT>A), RS1002172267 (10:27401329 A>T), RS1002338971 (10:27406525 T>A,G), RS1002549800 (10:27403502 T>C), RS1002671019 (10:27405388 C>T), RS1002718292 (10:27396939 A>C), RS1002813985 (10:27396639 G>A), RS1002913817 (10:27411099 T>C,G)

Disease associations

OMIM: gene MIM:611791 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001526_19	Fasting blood insulin (BMI interaction)	5.000000e-06
GCST002949_26	Epilepsy and lamotrigine-induced maculopapular eruptions	4.000000e-07
GCST003482_1	Asthma (childhood onset)	2.000000e-07
GCST004071_15	Cerebrospinal T-tau levels	7.000000e-06
GCST010566_6	Benign childhood epilepsy with centro-temporal spikes	2.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:1001253	maculopapular eruption
EFO:0004760	t-tau measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Phthalic Acids	increases methylation	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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