CACHD1

Summary

CACHD1 (cache domain containing 1, HGNC:29314) is a protein-coding gene on chromosome 1p31.3, encoding VWFA and cache domain-containing protein 1 (Q5VU97). May regulate voltage-dependent calcium channels.

Predicted to enable voltage-gated calcium channel activity. Predicted to be involved in calcium ion transmembrane transport. Predicted to be located in membrane. Predicted to be part of voltage-gated calcium channel complex.

Source: NCBI Gene 57685 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 196 total — 8 pathogenic
• MANE Select transcript: NM_020925

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29314
Approved symbol	CACHD1
Name	cache domain containing 1
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1573
Ensembl gene	ENSG00000158966
Ensembl biotype	protein_coding
OMIM	620144
Entrez	57685

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000290039, ENST00000470527, ENST00000486580, ENST00000495994, ENST00000650260, ENST00000651257, ENST00000892890, ENST00000934714, ENST00000934715, ENST00000934716, ENST00000945835

RefSeq mRNA: 2 — MANE Select: NM_020925 NM_001293274, NM_020925

CCDS: CCDS628

Canonical transcript exons

ENST00000651257 — 27 exons

Exon	Start	End
ENSE00003462517	64666057	64666167
ENSE00003465007	64673158	64673257
ENSE00003489012	64679595	64679756
ENSE00003494299	64652161	64652310
ENSE00003503806	64671564	64671686
ENSE00003509680	64602806	64602912
ENSE00003513555	64654686	64654803
ENSE00003514457	64641820	64641969
ENSE00003533059	64682005	64682106
ENSE00003537959	64550594	64550656
ENSE00003548245	64582156	64582304
ENSE00003554244	64664498	64664679
ENSE00003562157	64647801	64648034
ENSE00003585532	64681258	64681335
ENSE00003598060	64629355	64629481
ENSE00003621509	64653758	64653881
ENSE00003643357	64673348	64673464
ENSE00003649719	64663695	64663837
ENSE00003659502	64678159	64678310
ENSE00003664708	64658705	64658873
ENSE00003672124	64675897	64675983
ENSE00003673419	64675401	64675561
ENSE00003682668	64634044	64634260
ENSE00003686449	64676895	64677011
ENSE00003688493	64632599	64632743
ENSE00003843099	64470129	64470942
ENSE00003893340	64691323	64693053

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 98.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.3195 / max 376.4086, expressed in 1381 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3214	10.4771	1225
3217	1.2987	538
3216	0.9764	519
3213	0.7319	371
3215	0.4113	172
3221	0.2454	70
3222	0.1786	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	98.77	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.41	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.39	gold quality
parietal pleura	UBERON:0002400	94.42	gold quality
germinal epithelium of ovary	UBERON:0001304	93.44	gold quality
bronchial epithelial cell	CL:0002328	92.18	gold quality
bronchus	UBERON:0002185	91.74	gold quality
layer of synovial tissue	UBERON:0007616	91.03	gold quality
urethra	UBERON:0000057	90.84	gold quality
seminal vesicle	UBERON:0000998	90.04	gold quality
pigmented layer of retina	UBERON:0001782	89.59	gold quality
retina	UBERON:0000966	89.57	gold quality
visceral pleura	UBERON:0002401	89.50	gold quality
corpus epididymis	UBERON:0004359	89.50	gold quality
calcaneal tendon	UBERON:0003701	89.36	gold quality
fallopian tube	UBERON:0003889	89.17	gold quality
synovial joint	UBERON:0002217	89.15	gold quality
mammalian vulva	UBERON:0000997	89.09	gold quality
mammary duct	UBERON:0001765	89.04	gold quality
epithelium of mammary gland	UBERON:0003244	89.02	gold quality
ventricular zone	UBERON:0003053	88.99	gold quality
upper arm skin	UBERON:0004263	88.89	gold quality
pericardium	UBERON:0002407	88.83	gold quality
lateral globus pallidus	UBERON:0002476	88.77	gold quality
mammary gland	UBERON:0001911	88.38	gold quality
kidney epithelium	UBERON:0004819	88.37	silver quality
thoracic mammary gland	UBERON:0005200	88.33	gold quality
nasal cavity epithelium	UBERON:0005384	87.89	gold quality
parotid gland	UBERON:0001831	87.53	gold quality
medial globus pallidus	UBERON:0002477	87.13	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	65.65
E-ANND-3	yes	7.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting CACHD1, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-580-3P	99.67	69.23	1841

Literature-anchored findings (GeneRIF, showing 3)

• CACHD1 increases the presence of CaV3.1 at the cell surface and causes an increase in channel open probability. (PMID:30181139)
• CACHD1: A new activity-modifying protein for voltage-gated calcium channels (PMID:30983497)
• Biallelic loss-of-function variants in CACHD1 cause a novel neurodevelopmental syndrome with facial dysmorphism and multisystem congenital abnormalities. (PMID:38158856)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cachd1	ENSDARG00000061590
mus_musculus	Cachd1	ENSMUSG00000028532
rattus_norvegicus	Cachd1	ENSRNOG00000010514
drosophila_melanogaster	CG16868	FBGN0034498

Paralogs (4): CACNA2D2 (ENSG00000007402), CACNA2D4 (ENSG00000151062), CACNA2D1 (ENSG00000153956), CACNA2D3 (ENSG00000157445)

Protein

Protein identifiers

VWFA and cache domain-containing protein 1 — Q5VU97 (reviewed: Q5VU97)

All UniProt accessions (3): Q5VU97, A0A0A0MQY7, A0A3B3ISH2

UniProt curated annotations — full annotation on UniProt →

Function. May regulate voltage-dependent calcium channels.

Subcellular location. Membrane.

Similarity. Belongs to the calcium channel subunit alpha-2/delta family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VU97-1	1	yes
Q5VU97-2	2

RefSeq proteins (2): NP_001280203, NP_065976* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR029151	Sensor-like_sf	Homologous_superfamily
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR051173	Ca_channel_alpha-2/delta	Family

UniProt features (14 total): domain 3, topological domain 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1, sequence variant 1, sequence conflict 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VU97-F1	77.76	0.44

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): 145

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 134 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, PEREZ_TP63_TARGETS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, CHANDRAN_METASTASIS_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, MODULE_205, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, DOUGLAS_BMI1_TARGETS_UP, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, AACTGGA_MIR145, RIGGI_EWING_SARCOMA_PROGENITOR_UP, GOBP_TRANSMEMBRANE_TRANSPORT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN

GO Biological Process (3): monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (1): voltage-gated calcium channel activity (GO:0005245)

GO Cellular Component (2): voltage-gated calcium channel complex (GO:0005891), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
metal ion transport	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
calcium channel activity	1
voltage-gated monoatomic cation channel activity	1
calcium channel complex	1
plasma membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

718 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CACHD1	CAV3	P56539	622
CACHD1	ZNF841	Q6ZN19	543
CACHD1	MFSD6L	Q8IWD5	526
CACHD1	RAVER2	Q9HCJ3	517
CACHD1	ARMCX4	Q5H9R4	503
CACHD1	ZMYM6	O95789	476
CACHD1	TMEM259	Q4ZIN3	476
CACHD1	NECAB3	Q96P71	474
CACHD1	ZNF354A	O60765	461
CACHD1	AP4S1	Q9Y587	460
CACHD1	UBAC2	Q8NBM4	453
CACHD1	EMC1	Q8N766	445
CACHD1	TAX1BP3	O14907	438
CACHD1	RAB30	Q15771	436
CACHD1	SMPDL3B	Q92485	436

IntAct

51 interactions, top by confidence:

A	B	Type	Score
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
FAM131B	AURKA	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
CACHD1	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
CACHD1	BICRAL	psi-mi:“MI:0915”(physical association)	0.370
CACHD1	XAB2	psi-mi:“MI:0915”(physical association)	0.370
CACHD1	ZMIZ1	psi-mi:“MI:0915”(physical association)	0.370
CACHD1	RANBP10	psi-mi:“MI:0915”(physical association)	0.370
ZNG1B	TCERG1	psi-mi:“MI:0914”(association)	0.350
TMEM52B	PIK3R2	psi-mi:“MI:0914”(association)	0.350
SLAMF1	RTCA	psi-mi:“MI:0914”(association)	0.350
ST8SIA4	NRP1	psi-mi:“MI:0914”(association)	0.350
BTRC	ACOT7	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
ST8SIA4	FAM234B	psi-mi:“MI:0914”(association)	0.350
TMEM74	KLRG2	psi-mi:“MI:0914”(association)	0.350
CCL3	KRBA1	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	RTL8C	psi-mi:“MI:0914”(association)	0.350
C1orf54	AGRN	psi-mi:“MI:0914”(association)	0.350
FAM131B	UQCRQ	psi-mi:“MI:0914”(association)	0.350
PON2	ENTPD6	psi-mi:“MI:0914”(association)	0.350
TRGV3	MANBA	psi-mi:“MI:0914”(association)	0.350
GGH	MANBA	psi-mi:“MI:0914”(association)	0.350
FBXW11	BHLHE40	psi-mi:“MI:0914”(association)	0.350
PLPPR2	BCL2L1	psi-mi:“MI:0914”(association)	0.350

BioGRID (105): CACHD1 (Affinity Capture-MS), CACHD1 (Affinity Capture-MS), CACHD1 (Proximity Label-MS), CACHD1 (Proximity Label-MS), CACHD1 (Affinity Capture-MS), CACHD1 (Affinity Capture-MS), CACHD1 (Affinity Capture-MS), CACHD1 (Affinity Capture-MS), CACHD1 (Affinity Capture-MS), CACHD1 (Affinity Capture-MS), CACHD1 (Affinity Capture-MS), CACHD1 (Affinity Capture-MS), CACHD1 (Affinity Capture-RNA), CACHD1 (Proximity Label-MS), CACHD1 (Proximity Label-MS)

ESM2 similar proteins: A1A4K5, A4IID1, A7XY94, O08532, O54890, O77836, P05106, P13806, P18614, P26009, P54289, P54290, Q00960, Q01097, Q13224, Q13822, Q3V3R4, Q4R854, Q5M854, Q5NVB3, Q5R1P3, Q5REP8, Q5VU97, Q64610, Q659X0, Q6BEA0, Q6EV76, Q6EV77, Q6GMK0, Q6GQI7, Q6GQK9, Q6IS24, Q6NYS8, Q6PDJ1, Q6PHS9, Q7TT15, Q80UG2, Q812G0, Q86X52, Q8BFR2

Diamond homologs: P39214, P39217, Q5BI42, Q5VU97, Q6PDJ1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 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
NCAM signaling for neurite out-growth	5	31.6×	2e-05
RAF/MAP kinase cascade	5	7.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	0
Uncertain significance	156
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
4820568	NM_020925.4(CACHD1):c.1783-1G>A	Pathogenic
4820569	NM_020925.4(CACHD1):c.2387+1G>A	Pathogenic
4820570	NM_020925.4(CACHD1):c.261+2T>C	Pathogenic
4820571	NM_020925.4(CACHD1):c.648del (p.Ile217fs)	Pathogenic
4820572	NM_020925.4(CACHD1):c.274dup (p.Ile92fs)	Pathogenic
4820573	NM_020925.4(CACHD1):c.277C>T (p.Arg93Ter)	Pathogenic
4820574	NM_020925.4(CACHD1):c.460C>T (p.Arg154Ter)	Pathogenic
666427	Single allele	Pathogenic

SpliceAI

5139 predictions. Top by Δscore:

Variant	Effect	Δscore
1:64470938:TGCAG:T	donor_gain	1.0000
1:64470939:GCAG:G	donor_gain	1.0000
1:64470939:GCAGG:G	donor_gain	1.0000
1:64470940:CAG:C	donor_gain	1.0000
1:64470940:CAGGT:C	donor_loss	1.0000
1:64470941:AG:A	donor_gain	1.0000
1:64470941:AGGT:A	donor_loss	1.0000
1:64470942:GG:G	donor_gain	1.0000
1:64470943:G:GG	donor_gain	1.0000
1:64470943:GT:G	donor_loss	1.0000
1:64550587:A:AG	acceptor_gain	1.0000
1:64550592:A:AG	acceptor_gain	1.0000
1:64550592:AGC:A	acceptor_gain	1.0000
1:64550592:AGCG:A	acceptor_gain	1.0000
1:64550593:G:GC	acceptor_gain	1.0000
1:64550593:GC:G	acceptor_gain	1.0000
1:64550593:GCG:G	acceptor_gain	1.0000
1:64550593:GCGG:G	acceptor_gain	1.0000
1:64550652:AGCAG:A	donor_loss	1.0000
1:64550653:GCAG:G	donor_gain	1.0000
1:64550653:GCAGG:G	donor_loss	1.0000
1:64550654:CAGG:C	donor_loss	1.0000
1:64550655:AG:A	donor_loss	1.0000
1:64550656:GGTA:G	donor_loss	1.0000
1:64550657:G:T	donor_loss	1.0000
1:64550658:T:G	donor_loss	1.0000
1:64550664:GCAA:G	donor_gain	1.0000
1:64552076:GGATA:G	donor_gain	1.0000
1:64582155:GCTA:G	acceptor_gain	1.0000
1:64582302:G:GT	donor_gain	1.0000

AlphaMissense

8468 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:64582276:T:C	C128R	1.000
1:64582277:G:A	C128Y	1.000
1:64582278:C:G	C128W	1.000
1:64602849:T:A	C152S	1.000
1:64602849:T:C	C152R	1.000
1:64602850:G:A	C152Y	1.000
1:64602850:G:C	C152S	1.000
1:64602851:T:G	C152W	1.000
1:64629393:T:A	W186R	1.000
1:64629393:T:C	W186R	1.000
1:64629395:G:C	W186C	1.000
1:64629395:G:T	W186C	1.000
1:64629436:C:A	P200Q	1.000
1:64647905:G:C	G421R	1.000
1:64652211:G:A	G481R	1.000
1:64652211:G:C	G481R	1.000
1:64652212:G:A	G481E	1.000
1:64652212:G:T	G481V	1.000
1:64652293:T:C	F508S	1.000
1:64652296:T:C	L509P	1.000
1:64654789:T:G	Y590D	1.000
1:64654795:T:A	W592R	1.000
1:64654795:T:C	W592R	1.000
1:64658729:T:C	C603R	1.000
1:64658731:T:G	C603W	1.000
1:64658814:G:C	R631P	1.000
1:64663793:T:G	Y684D	1.000
1:64663797:T:C	L685P	1.000
1:64663802:G:C	D687H	1.000
1:64663803:A:T	D687V	1.000

dbSNP variants (sampled 300 via entrez): RS1000002556 (1:64593408 A>C,G), RS1000019579 (1:64637245 G>A), RS1000021015 (1:64621515 A>C,G), RS1000055937 (1:64586518 C>T), RS1000063171 (1:64681142 T>G), RS1000067059 (1:64549336 C>A,T), RS1000074178 (1:64631058 G>A), RS1000100476 (1:64543567 C>T), RS1000141955 (1:64587833 G>C), RS1000153926 (1:64567454 A>C), RS1000189122 (1:64662071 A>C), RS1000190623 (1:64523828 C>G,T), RS1000194405 (1:64492637 G>A,T), RS1000198861 (1:64674400 T>C), RS1000208107 (1:64568483 G>GAAAA)

Disease associations

OMIM: gene MIM:620144 | 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
GCST90006987_1	Gut microbiota relative abundance (Bifidobacterium)	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	6
trichostatin A	affects cotreatment, decreases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
titanium dioxide	increases methylation	1
arsenite	decreases methylation	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	decreases expression, affects binding	1
(+)-JQ1 compound	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	affects binding, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression, decreases reaction	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A9SX	BL1391	Cancer cell line	Female

Clinical trials (associated diseases)

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