CALHM5

Summary

CALHM5 (calcium homeostasis modulator family member 5, HGNC:21568) is a protein-coding gene on chromosome 6q22.1, encoding Calcium homeostasis modulator protein 5 (Q8N5C1). May assemble to form large pore channels with gating and ion conductance likely regulated by membrane lipids.

Predicted to enable monoatomic cation channel activity. Predicted to be involved in ATP export and monoatomic cation transmembrane transport. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 254228 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_153711

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21568
Approved symbol	CALHM5
Name	calcium homeostasis modulator family member 5
Location	6q22.1
Locus type	gene with protein product
Status	Approved
Aliases	dJ493F7.3, MGC45451
Ensembl gene	ENSG00000178033
Ensembl biotype	protein_coding
Entrez	254228

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000368599

RefSeq mRNA: 1 — MANE Select: NM_153711 NM_153711

CCDS: CCDS5108

Canonical transcript exons

ENST00000368599 — 2 exons

Exon	Start	End
ENSE00001447525	116515600	116524788
ENSE00001447526	116511639	116512236

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 87.80.

FANTOM5 (CAGE): breadth broad, TPM avg 5.2212 / max 119.6918, expressed in 889 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69428	2.4546	666
69427	2.2543	700
69426	0.5123	328

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	87.80	gold quality
tendon	UBERON:0000043	81.46	gold quality
thoracic aorta	UBERON:0001515	79.54	gold quality
calcaneal tendon	UBERON:0003701	79.48	gold quality
ascending aorta	UBERON:0001496	79.38	gold quality
descending thoracic aorta	UBERON:0002345	79.31	gold quality
cardiac muscle of right atrium	UBERON:0003379	78.46	gold quality
left ventricle myocardium	UBERON:0006566	78.20	gold quality
epithelial cell of pancreas	CL:0000083	77.45	gold quality
right coronary artery	UBERON:0001625	77.40	gold quality
aorta	UBERON:0000947	77.22	gold quality
left coronary artery	UBERON:0001626	76.35	gold quality
coronary artery	UBERON:0001621	76.03	gold quality
stromal cell of endometrium	CL:0002255	75.58	gold quality
myocardium	UBERON:0002349	75.58	gold quality
popliteal artery	UBERON:0002250	75.53	gold quality
tibial artery	UBERON:0007610	75.51	gold quality
saphenous vein	UBERON:0007318	74.90	gold quality
mucosa of paranasal sinus	UBERON:0005030	74.14	gold quality
kidney epithelium	UBERON:0004819	73.91	gold quality
pancreatic ductal cell	CL:0002079	73.12	silver quality
buccal mucosa cell	CL:0002336	72.63	gold quality
placenta	UBERON:0001987	71.24	gold quality
apex of heart	UBERON:0002098	70.71	gold quality
medial globus pallidus	UBERON:0002477	70.24	silver quality
smooth muscle tissue	UBERON:0001135	69.57	gold quality
subcutaneous adipose tissue	UBERON:0002190	69.37	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	69.01	silver quality
quadriceps femoris	UBERON:0001377	68.88	gold quality
adipose tissue	UBERON:0001013	68.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

257 targeting CALHM5, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4789-3P	99.99	70.75	2484

Literature-anchored findings (GeneRIF, showing 1)

• Human CALHM5: Insight in large pore lipid gating ATP channel and associated neurological pathologies. (PMID:34089472)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	calhm5.2	ENSDARG00000012726
danio_rerio	calhm5.1	ENSDARG00000074947
mus_musculus	Calhm5	ENSMUSG00000049872
rattus_norvegicus	Calhm5	ENSRNOG00000000825
caenorhabditis_elegans		WBGENE00016626

Paralogs (5): CALHM2 (ENSG00000138172), CALHM4 (ENSG00000164451), CALHM3 (ENSG00000183128), CALHM1 (ENSG00000185933), CALHM6 (ENSG00000188820)

Protein

Protein identifiers

Calcium homeostasis modulator protein 5 — Q8N5C1 (reviewed: Q8N5C1)

Alternative names: Protein FAM26E

All UniProt accessions (1): Q8N5C1

UniProt curated annotations — full annotation on UniProt →

Function. May assemble to form large pore channels with gating and ion conductance likely regulated by membrane lipids.

Subunit / interactions. Oligomerizes to form undecameric cone-shaped channels.

Subcellular location. Membrane.

Similarity. Belongs to the CALHM family.

RefSeq proteins (1): NP_714922* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029569	CALHM	Family

Pfam: PF14798

UniProt features (43 total): helix 17, binding site 6, topological domain 5, transmembrane region 4, strand 4, disulfide bond 3, turn 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7D60	ELECTRON MICROSCOPY	2.61
7D61	ELECTRON MICROSCOPY	2.8
7D65	ELECTRON MICROSCOPY	2.94

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5C1-F1	90.42	0.79

Functional residue map

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

Ligand- & substrate-binding residues (6): 15; 32; 37; 102; 121; 202

Disulfide bonds (3): 41–127, 43–158, 142–149

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 110 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GGGTGGRR_PAX4_03, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, MARTINEZ_RB1_TARGETS_UP, TGCTGAY_UNKNOWN, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, TGACATY_UNKNOWN, GOBP_PURINE_NUCLEOTIDE_TRANSPORT, GATA1_04, NKX22_01, FREAC4_01, GATA1_02

GO Biological Process (4): ATP export (GO:1904669), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (2): monoatomic cation channel activity (GO:0005261), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP transport	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
monoatomic ion channel activity	1
monoatomic cation transmembrane transporter activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

258 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CALHM5	NT5DC1	Q5TFE4	500
CALHM5	ZNF841	Q6ZN19	446
CALHM5	LBH	Q53QV2	417
CALHM5	CYB5D1	Q6P9G0	390
CALHM5	FRMPD1	Q5SYB0	367
CALHM5	GGT5	P36269	356
CALHM5	PAMR1	Q6UXH9	346
CALHM5	CSRP1	P21291	333
CALHM5	FILIP1	Q7Z7B0	329
CALHM5	IBTK	Q9P2D0	318
CALHM5	GSTCD	Q8NEC7	299
CALHM5	CALHM4	Q5JW98	297
CALHM5	GLCCI1	Q86VQ1	294
CALHM5	FBXO3	Q9UK99	294
CALHM5	RCN2	Q14257	293

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CALHM5	CDK6	psi-mi:“MI:0915”(physical association)	0.590
CALHM5	LRP10	psi-mi:“MI:0915”(physical association)	0.400
CFTR	CALHM5	psi-mi:“MI:0915”(physical association)	0.370
ST7	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): CDK6 (Affinity Capture-MS), FAM26E (Affinity Capture-MS), CDK6 (Affinity Capture-MS), LRP10 (Affinity Capture-MS), FAM26E (PCA), FAM26E (Proximity Label-MS)

ESM2 similar proteins: A0A140LIJ0, A1L3G9, A4IFL1, B9X187, O18968, O70491, P08033, P08034, P28230, P35212, P36380, P51915, P60572, Q02738, Q059Y8, Q0V8E7, Q1LXZ7, Q28FG4, Q29559, Q4QR83, Q5E9Z5, Q5FVF4, Q5FWS4, Q5JW98, Q5R7B4, Q5T197, Q5T1A1, Q60HF7, Q640M6, Q6GMB1, Q6WGK6, Q7SY10, Q7TNJ0, Q8BXV2, Q8C2L6, Q8C9E8, Q8CE93, Q8CEG0, Q8N5C1, Q8NDZ6

Diamond homologs: A4FUN9, Q561R8, Q5FWS4, Q5JW98, Q5R3K3, Q8C9E8, Q8CE93, Q8N5C1, Q8R100, J3QMI4, Q2HJ63, Q5RJQ8, Q86XJ0, Q8VEC4, Q9HA72, D3Z291, Q8IU99

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

393 predictions. Top by Δscore:

Variant	Effect	Δscore
6:116512232:CTCAG:C	donor_loss	0.9900
6:116512233:TCAG:T	donor_loss	0.9900
6:116512234:CAGGT:C	donor_loss	0.9900
6:116512235:AGGT:A	donor_loss	0.9900
6:116512236:GGTA:G	donor_loss	0.9900
6:116512237:GTAA:G	donor_loss	0.9900
6:116512238:T:G	donor_loss	0.9900
6:116515654:T:G	acceptor_gain	0.9800
6:116511808:GCTTT:G	donor_gain	0.9700
6:116515598:A:G	acceptor_gain	0.9700
6:116515598:AGATT:A	acceptor_loss	0.9700
6:116515599:G:A	acceptor_loss	0.9700
6:116515599:GA:G	acceptor_gain	0.9700
6:116515768:C:G	donor_gain	0.9700
6:116512125:GG:G	donor_gain	0.9600
6:116512126:GG:G	donor_gain	0.9600
6:116511782:G:T	donor_gain	0.9500
6:116514213:G:T	donor_gain	0.9400
6:116512491:T:G	donor_gain	0.9200
6:116515599:G:GC	acceptor_gain	0.9200
6:116511782:G:GT	donor_gain	0.9100
6:116512237:G:GG	donor_gain	0.8900
6:116515779:G:GT	donor_gain	0.8800
6:116515597:A:AG	acceptor_gain	0.8700
6:116515599:GAT:G	acceptor_gain	0.8500
6:116515969:G:A	donor_gain	0.8400
6:116511785:G:GG	donor_gain	0.8000
6:116515599:GATT:G	acceptor_gain	0.7900
6:116512122:CAAGG:C	donor_loss	0.7800
6:116512123:AAGGG:A	donor_loss	0.7800

AlphaMissense

2042 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:116511757:A:C	S21R	0.991
6:116511759:C:A	S21R	0.991
6:116511759:C:G	S21R	0.991
6:116511811:T:C	F39L	0.990
6:116511813:T:A	F39L	0.990
6:116511813:T:G	F39L	0.990
6:116512036:T:A	W114R	0.987
6:116512036:T:C	W114R	0.987
6:116515843:T:A	W262R	0.985
6:116515843:T:C	W262R	0.985
6:116515609:T:A	W184R	0.982
6:116515609:T:C	W184R	0.982
6:116515845:G:C	W262C	0.980
6:116515845:G:T	W262C	0.980
6:116512084:A:C	S130R	0.978
6:116512086:C:A	S130R	0.978
6:116512086:C:G	S130R	0.978
6:116515894:A:C	S279R	0.978
6:116515896:C:A	S279R	0.978
6:116515896:C:G	S279R	0.978
6:116512075:T:A	C127S	0.976
6:116512076:G:C	C127S	0.976
6:116511784:A:C	S30R	0.974
6:116511786:T:A	S30R	0.974
6:116511786:T:G	S30R	0.974
6:116515784:T:C	L242P	0.974
6:116511856:T:C	F54L	0.973
6:116511858:C:A	F54L	0.973
6:116511858:C:G	F54L	0.973
6:116515699:T:C	F214L	0.973

dbSNP variants (sampled 300 via entrez): RS1000148544 (6:116517635 G>A,T), RS1000343394 (6:116521338 G>A,T), RS1000378580 (6:116514237 A>G), RS1000543462 (6:116521197 A>G), RS1000914622 (6:116520958 T>C), RS1001120923 (6:116515647 C>T), RS1001510316 (6:116513891 A>G), RS1001719054 (6:116520541 G>A,C,T), RS1001971424 (6:116521245 T>C), RS1002456311 (6:116522141 G>A,T), RS1002511331 (6:116512326 T>C), RS1002545406 (6:116518140 T>C), RS1002560738 (6:116514552 A>G), RS1002646525 (6:116510889 T>C), RS1002696403 (6:116524633 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
bisphenol A	increases expression, increases methylation, affects cotreatment	3
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	3
Benzo(a)pyrene	decreases expression, increases expression	2
Cadmium	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
ethyl-p-hydroxybenzoate	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
zinc chromate	increases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Arsenic	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Triclosan	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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