CAMKMT

Summary

CAMKMT (calmodulin-lysine N-methyltransferase, HGNC:26276) is a protein-coding gene on chromosome 2p21, encoding Calmodulin-lysine N-methyltransferase (Q7Z624). Catalyzes the trimethylation of ‘Lys-116’ in calmodulin.

This gene encodes a class I protein methyltransferase that acts in the formation of trimethyllysine in calmodulin. The protein contains a AdoMet-binding motif and may play a role in calcium-dependent signaling.

Source: NCBI Gene 79823 — RefSeq curated summary.

At a glance

• GWAS associations: 26 (top 5% of genes corpus-wide)
• Clinical variants (ClinVar): 87 total — 4 pathogenic
• GTEx eGene: eQTL in 29 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 19
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.64 (unconstrained)
• MANE Select transcript: NM_024766
• Notable: 87 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26276
Approved symbol	CAMKMT
Name	calmodulin-lysine N-methyltransferase
Location	2p21
Locus type	gene with protein product
Status	Approved
Aliases	CLNMT
Ensembl gene	ENSG00000143919
Ensembl biotype	protein_coding
OMIM	609559
Entrez	79823

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 10 protein_coding, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000378494

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 4, TSL 4: 1, TSL 5: 1

ENST00000378494, ENST00000402247, ENST00000403853, ENST00000407131, ENST00000428929, ENST00000428993, ENST00000454433, ENST00000477623, ENST00000477830, ENST00001002530, ENST00001002531, ENST00001002532, ENST00001060062, ENST00001096871, ENST00001118955, ENST00001130408, ENST00001142930

RefSeq mRNA: 1 — MANE Select: NM_024766 NM_024766

CCDS: CCDS1820

Canonical transcript exons

ENST00000378494 — 11 exons

Exon	Start	End
ENSE00001159027	44372716	44372888
ENSE00001298716	44766430	44766561
ENSE00001308254	44754055	44754118
ENSE00001329032	44743622	44743696
ENSE00001477705	44772036	44772592
ENSE00003498715	44707399	44707462
ENSE00003539666	44706287	44706341
ENSE00003570049	44715287	44715353
ENSE00003591328	44390241	44390305
ENSE00003647584	44704283	44704343
ENSE00003850095	44361947	44362145

Expression profiles

Bgee: expression breadth ubiquitous, 223 present calls, max score 84.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.6013 / max 312.3710, expressed in 1762 samples.

Highest expression (Bgee): nucleus accumbens, testis, male germ line stem cell (sensu Vertebrata) in testis, cranial nerve II, anterior cingulate cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CAMKMT is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	sqtl	3.3e-33	-1.60	2:44392022:G:A
Muscle Skeletal	sqtl	2.5e-15	-0.83	2:44392022:G:A
Heart Atrial Appendage	eqtl	1.7e-11	+0.88	2:44362007:G:A
Skin Not Sun Exposed Suprapubic	eqtl	7.2e-11	+0.59	2:44362007:G:A
Adipose Subcutaneous	eqtl	2.9e-09	+0.58	2:44440826:AT:A
Thyroid	eqtl	2.6e-08	+0.40	2:44587784:A:G
Esophagus Mucosa	eqtl	5.1e-08	+0.72	2:44362007:G:A
Skin Sun Exposed Lower leg	eqtl	1.2e-07	+0.46	2:44362007:G:A
Muscle Skeletal	eqtl	1.3e-07	+0.49	2:44362007:G:A
Testis	eqtl	3.9e-07	-0.34	2:44464148:A:C
Cells EBV-transformed lymphocytes	sqtl	9.5e-07	-0.70	2:44372125:A:G
Whole Blood	eqtl	1.2e-06	-0.21	2:44563383:C:A
Cells Cultured fibroblasts	eqtl	4.3e-06	-0.35	2:44586955:TG:T
Heart Left Ventricle	eqtl	7.1e-06	+0.58	2:44362007:G:A
Nerve Tibial	eqtl	7.3e-05	-0.21	2:44711229:G:C
Brain Caudate basal ganglia	eqtl	7.6e-05	-0.34	2:44704381:C:T
Colon Transverse	eqtl	8.1e-05	-0.24	2:44610076:G:C
Pancreas	eqtl	2.7e-04	-0.51	2:44658861:A:C
Breast Mammary Tissue	eqtl	3.7e-04	+0.60	2:44362007:G:A
Prostate	eqtl	4.6e-04	-0.37	2:44547916:G:C

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
19999	9.0307	1759
20007	0.2050	12
20001	0.1338	39
20005	0.1228	6
20000	0.0837	16
20006	0.0254	3

Top tissues by expression

showing 100 of 272 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	84.99	gold quality
left testis	UBERON:0004533	84.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.12	gold quality
right testis	UBERON:0004534	83.79	gold quality
cranial nerve II	UBERON:0000941	83.16	gold quality
anterior cingulate cortex	UBERON:0009835	83.13	gold quality
caudate nucleus	UBERON:0001873	83.06	gold quality
cingulate cortex	UBERON:0003027	83.06	gold quality
calcaneal tendon	UBERON:0003701	82.89	gold quality
putamen	UBERON:0001874	82.72	gold quality
testis	UBERON:0000473	82.44	gold quality
gastrocnemius	UBERON:0001388	81.80	gold quality
body of pancreas	UBERON:0001150	81.66	gold quality
right frontal lobe	UBERON:0002810	81.54	gold quality
lower esophagus mucosa	UBERON:0035834	81.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.14	gold quality
muscle of leg	UBERON:0001383	81.10	gold quality
amygdala	UBERON:0001876	80.66	gold quality
mucosa of transverse colon	UBERON:0004991	80.43	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.18	gold quality
hypothalamus	UBERON:0001898	79.99	gold quality
prefrontal cortex	UBERON:0000451	79.90	gold quality
pancreas	UBERON:0001264	79.80	gold quality
monocyte	CL:0000576	79.34	gold quality
colonic epithelium	UBERON:0000397	79.24	gold quality
cerebellar cortex	UBERON:0002129	79.21	gold quality
cerebellar hemisphere	UBERON:0002245	79.20	gold quality
mononuclear cell	CL:0000842	79.18	gold quality
descending thoracic aorta	UBERON:0002345	79.15	gold quality
thoracic aorta	UBERON:0001515	79.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.14	gold quality
leukocyte	CL:0000738	79.07	gold quality
ascending aorta	UBERON:0001496	78.97	gold quality
corpus callosum	UBERON:0002336	78.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	78.96	gold quality
aorta	UBERON:0000947	78.86	gold quality
left coronary artery	UBERON:0001626	78.82	gold quality
popliteal artery	UBERON:0002250	78.80	gold quality
telencephalon	UBERON:0001893	78.79	gold quality
tibial artery	UBERON:0007610	78.78	gold quality
apex of heart	UBERON:0002098	78.75	gold quality
neocortex	UBERON:0001950	78.49	gold quality
forebrain	UBERON:0001890	78.43	gold quality
metanephros cortex	UBERON:0010533	78.42	gold quality
cerebellum	UBERON:0002037	78.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.23	gold quality
right adrenal gland	UBERON:0001233	78.14	gold quality
brain	UBERON:0000955	78.07	gold quality
islet of Langerhans	UBERON:0000006	78.00	gold quality
right adrenal gland cortex	UBERON:0035827	77.99	gold quality
frontal cortex	UBERON:0001870	77.98	gold quality
substantia nigra	UBERON:0002038	77.88	gold quality
coronary artery	UBERON:0001621	77.77	gold quality
rectum	UBERON:0001052	77.71	gold quality
tendon	UBERON:0000043	77.55	gold quality
spinal cord	UBERON:0002240	77.49	gold quality
cerebral cortex	UBERON:0000956	77.46	gold quality
left adrenal gland	UBERON:0001234	77.46	gold quality
adrenal tissue	UBERON:0018303	77.46	gold quality
esophagus mucosa	UBERON:0002469	77.37	gold quality
left adrenal gland cortex	UBERON:0035825	77.21	gold quality
oocyte	CL:0000023	77.12	gold quality
body of stomach	UBERON:0001161	77.04	gold quality
right atrium auricular region	UBERON:0006631	76.99	gold quality
gall bladder	UBERON:0002110	76.97	gold quality
ectocervix	UBERON:0012249	76.94	gold quality
adrenal gland	UBERON:0002369	76.92	gold quality
stomach	UBERON:0000945	76.81	gold quality
adenohypophysis	UBERON:0002196	76.52	gold quality
skin of abdomen	UBERON:0001416	76.50	gold quality
midbrain	UBERON:0001891	76.47	gold quality
right coronary artery	UBERON:0001625	76.40	gold quality
temporal lobe	UBERON:0001871	76.37	gold quality
adrenal cortex	UBERON:0001235	76.35	gold quality
esophagus	UBERON:0001043	76.31	gold quality
skin of leg	UBERON:0001511	76.31	gold quality
tonsil	UBERON:0002372	76.31	gold quality
secondary oocyte	CL:0000655	76.28	gold quality
granulocyte	CL:0000094	76.25	gold quality
stromal cell of endometrium	CL:0002255	76.25	gold quality
left lobe of thyroid gland	UBERON:0001120	76.19	gold quality
pigmented layer of retina	UBERON:0001782	76.09	gold quality
Ammon’s horn	UBERON:0001954	75.90	gold quality
transverse colon	UBERON:0001157	75.83	gold quality
ventricular zone	UBERON:0003053	75.82	gold quality
thyroid gland	UBERON:0002046	75.64	gold quality
right lobe of thyroid gland	UBERON:0001119	75.63	gold quality
heart left ventricle	UBERON:0002084	75.62	gold quality
endocervix	UBERON:0000458	75.36	gold quality
muscle organ	UBERON:0001630	75.30	gold quality
cardiac atrium	UBERON:0002081	75.22	gold quality
right lobe of liver	UBERON:0001114	75.18	gold quality
lower esophagus	UBERON:0013473	75.13	gold quality
lower esophagus muscularis layer	UBERON:0035833	75.10	gold quality
cardiac ventricle	UBERON:0002082	75.09	gold quality
omental fat pad	UBERON:0010414	75.07	gold quality
peritoneum	UBERON:0002358	75.04	gold quality
pituitary gland	UBERON:0000007	75.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	74.98	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.32
E-ENAD-17	no	642.82

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Nucleus accumbens	tissue	29.9
Choroid plexus	tissue	23.7
Postcentral gyrus	tissue	21.1
Locus coeruleus	tissue	17.5
Hippocampus	tissue	16.6
Hypothalamus	tissue	12.8
Testis	tissue	12.1
Periaqueductal gray	tissue	11.3
Pons	tissue	10.5
Septum	tissue	10.2
Thalamus	tissue	9.8
Midbrain	tissue	9.6
Superior colliculi	tissue	9.4
Pancreas	tissue	9.2
Basal ganglia	tissue	9.2
Substantia nigra	tissue	9.2
Parathyroid gland	tissue	9.1
Medulla oblongata	tissue	9.1
Ventral forebrain	tissue	8.9
Cerebellum	tissue	8.5
Spinal cord	tissue	8.5
Amygdala	tissue	8.3
Bone marrow	tissue	8.2
Putamen	tissue	8.1
Retina	tissue	7.6
Hippocampal formation	tissue	7.5
Cerebral cortex	tissue	7.2
Retrosplenial and cingulate cortex	tissue	7.2
Olfactory bulb	tissue	7.2
Prefrontal cortex	tissue	7.1
Skeletal muscle	tissue	7.0
Entorhinal cortex	tissue	7.0
Insular cortex	tissue	7.0
Caudate putamen	tissue	6.9
Motor cortex	tissue	6.8
Frontal cortex	tissue	6.8
Retrosplenial cortex	tissue	6.8
Temporal cortex	tissue	6.8
Thyroid gland	tissue	6.6
Occipital cortex	tissue	6.6
Somatosensory cortex	tissue	6.5
Colon	tissue	6.3
Kidney	tissue	6.3
Epididymis	tissue	6.2
Corpus callosum	tissue	6.1
Rectum	tissue	5.9
Thymus	tissue	5.6
Small intestine	tissue	5.3
Pituitary gland	tissue	5.2
Gallbladder	tissue	5.2
Cervix	tissue	5.1
Duodenum	tissue	5.0
Breast	tissue	4.7
Tonsil	tissue	4.7
Skin 1	tissue	4.5
Lymph node	tissue	4.5
Esophagus	tissue	4.4
Salivary gland	tissue	4.4
Stomach 1	tissue	4.3
Vagina	tissue	4.3

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Cerebellar cortex (26.8), Corpus callosum, genu (white matter) (26.4), Vermis (26.3), Parieto-temporal junction (white matter) (26.1), Flocculonodular lobe (24.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CAMKMT by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

26 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-6883-3P	97.97	67.35	643
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-1468-5P	94.18	69.04	176
HSA-MIR-136-3P	93.27	66.31	131

Functional genomics

gnomAD constraint: pLI 1.15e-11, LOEUF 1.64, missense Z -1.02 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000378494 — one region, missense o/e 1.06.

Literature-anchored findings (GeneRIF, showing 5)

• a deletion of C2orf34 causes atypical hypotonia-cystinuria syndrome (PMID:18234729)
• Two key transcription factors, NRF-2 and YY-1, were further identified to coordinately participate in driving gene expressions of PREPL-C2ORF34 genes pairin an additive manner. (PMID:19575798)
• Calmodulin methyltransferase is an evolutionarily conserved enzyme that trimethylates Lys-115 in calmodulin. (PMID:20975703)
• The CaM KMT is the major, possibly the single, methyltransferase of calmodulin in human cells with a wide tissue distribution and is a novel Hsp90 client protein. (PMID:23285036)
• Deletion of CAMKMT is associated with Hypotonia-cystinuria syndrome. (PMID:23794250)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	camkmt	ENSDARG00000091900
danio_rerio	camkmt	ENSDARG00000095224
mus_musculus	Camkmt	ENSMUSG00000071037
rattus_norvegicus	Camkmt	ENSRNOG00000030629
drosophila_melanogaster	CG10947	FBGN0032857

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1920832) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 14 distinct phenotype terms.

Mouse phenotype (MP)	Records
myopathy	1
decreased body weight	1
impaired coordination	1
increased mean platelet volume	1
impaired passive avoidance behavior	1
abnormal behavior	1
increased circulating creatinine level	1
increased blood urea nitrogen level	1
increased circulating sodium level	1
increased variability of skeletal muscle fiber size	1
decreased total body fat amount	1
decreased grip strength	1
abnormal mitochondrial ATP synthesis coupled electron transport	1
behavioral developmental delay	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Xenopus laevis	Q6GQ33	76.3%	Diamond
Arabidopsis thaliana	F4JNX3	32.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PPM1B-DT	ncRNA	102723904
PPM1B	protein-coding	5495
SLC3A1	protein-coding	6519
PREPL	protein-coding	9581
SIX3-AS1	ncRNA	100506108
LINC01833	ncRNA	107985879
SIX3	protein-coding	6496

Protein

Protein identifiers

Calmodulin-lysine N-methyltransferase — Q7Z624 (reviewed: Q7Z624)

All UniProt accessions (6): B5MC16, B5MC79, H7C2N4, H7C2T0, H7C3B0, Q7Z624

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the trimethylation of ‘Lys-116’ in calmodulin.

Subunit / interactions. Monomer. Interacts with HSP90, probably as a client.

Subcellular location. Cytoplasm. Nucleus Golgi apparatus.

Tissue specificity. Isoform 1 is expressed in brain, liver, muscle colon and lung. Isoform 2 is expressed in colon, testis, kidney and brain. Isoform 1 and isoform 2 are expressed in normal lymphoblastoid cells but not in lymphoblastoid cells from patients with hypotonia-cystinuria syndrome.

Disease relevance. Hypotonia-cystinuria syndrome (HCS) [MIM:606407] Characterized generalized hypotonia at birth, nephrolithiasis, growth hormone deficiency, minor facial dysmorphism, failure to thrive, followed by hyperphagia and rapid weight gain in late childhood. The gene represented in this entry is involved in disease pathogenesis. A homozygous 77.4-kb deletion that disrupts the gene represented in this entry, PREPL, and SLC3A1, causes atypical hypotonia-cystinuria syndrome, characterized by mild to moderate intellectual disability and respiratory chain complex IV deficiency.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. CLNMT methyltransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q7Z624-1	1	yes
Q7Z624-2	2

RefSeq proteins (1): NP_079042* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019410	Methyltransf_16	Family
IPR025800	CaM-Lys-N-MeTrfase	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily

Pfam: PF10294

Enzyme classification (BRENDA)

• EC 2.1.1.60 — calmodulin-lysine N-methyltransferase (BRENDA: 8 organisms, 15 substrates, 10 inhibitors, 8 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
S-ADENOSYL-L-METHIONINE	0.0008–0.002	3
CALMODULIN	—	1
MUSHROOM DEMETHYLCALMODULIN	0.0002	1
OCTOPUS CALMODULIN	—	1
VU-1 CALMODULIN	0.0001	1

Catalyzed reactions (Rhea)

• [calmodulin]-L-lysine + S-adenosyl-L-methionine = [calmodulin]-N(6)-methyl-L-lysine + S-adenosyl-L-homocysteine + H(+) (RHEA:21556)

UniProt features (31 total): helix 11, strand 10, turn 4, splice variant 2, chain 1, region of interest 1, compositionally biased region 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
4PWY	Crystal structure of a Calmodulin-lysine N-methyltransferase fragment	X-RAY DIFFRACTION	1.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z624-F1	85.97	0.69

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Predicted intracellular proteins, Disease related genes, Potential drug targets

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; nucleoli

Antibody reliability (HPA): IF supported

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade	curated
R-HSA-8876725	Protein methylation	curated
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-9709957	Sensory Perception	—
R-HSA-2514856	The phototransduction cascade	—
R-HSA-2187338	Visual phototransduction	—

MSigDB gene sets: 170 (showing top): GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_PHOTOTRANSDUCTION, YY1_Q6, MODULE_205, GOBP_PHOTOTRANSDUCTION_VISIBLE_LIGHT, GOBP_RESPONSE_TO_RADIATION, CCCNNNNNNAAGWT_UNKNOWN, GOBP_DETECTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_DETECTION_OF_STIMULUS, GOBP_CELLULAR_RESPONSE_TO_RADIATION, GOBP_METHYLATION, GOBP_RESPONSE_TO_LIGHT_STIMULUS

GO Biological Process (3): protein methylation (GO:0006479), regulation of opsin-mediated signaling pathway (GO:0022400), methylation (GO:0032259)

GO Molecular Function (4): calmodulin-lysine N-methyltransferase activity (GO:0018025), heat shock protein binding (GO:0031072), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (7): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), protein-containing complex (GO:0032991), nucleus (GO:0005634)

Reactome top-level categories

5 top-level categories:

Category	Pathways
The phototransduction cascade	1
Post-translational protein modification	1
Sensory Perception	1
Visual phototransduction	1
Metabolism of proteins	1

GO top-level categories

18 GO namespaces:

Category	Terms
cellular anatomical structure	3
nuclear lumen	2
cytoplasm	2
intracellular membrane-bounded organelle	2
protein alkylation	1
macromolecule methylation	1
regulation of G protein-coupled receptor signaling pathway	1
G protein-coupled opsin signaling pathway	1
regulation of response to external stimulus	1
metabolic process	1
protein-lysine N-methyltransferase activity	1
protein binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
endomembrane system	1
cellular_component	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 14 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
cytoplasm	CC	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
protein-containing complex	CC	direct assay
heat shock protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,026 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAMKMT	PREPL	Q4J6C6	962
CAMKMT	PPM1B	O75688	943
CAMKMT	SLC3A1	Q07837	929
CAMKMT	H3-3A	P06351	662
CAMKMT	H3C14	Q71DI3	662
CAMKMT	H3-5	Q6NXT2	662
CAMKMT	H3C1	P02295	662
CAMKMT	H3-4	Q16695	662
CAMKMT	H3-7	Q5TEC6	662
CAMKMT	NDC80	O14777	653
CAMKMT	METTL21A	Q8WXB1	643
CAMKMT	METTL22	Q9BUU2	625
CAMKMT	ETFBKMT	Q8IXQ9	622
CAMKMT	EHMT2	Q96KQ7	621
CAMKMT	DOT1L	Q8TEK3	609

IntAct

Human interaction partners of CAMKMT in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
COL1A1	association	0.530	2
H1-5	physical association	0.400	1
SELENBP1	association	0.350	1

BioGRID (49 interactions; top human partners by supporting records): COL1A1 (Affinity Capture-MS; 3 records), COL1A2 (Affinity Capture-MS; 3 records), FEM1B (Affinity Capture-MS; 3 records), HECTD1 (Affinity Capture-MS; 3 records), SNX6 (Affinity Capture-MS; 3 records), IREB2 (Affinity Capture-MS; 2 records), SELENBP1 (Affinity Capture-MS; 2 records), SPATA5L1 (Affinity Capture-MS; 2 records), AMBRA1 (Affinity Capture-MS), APP (Reconstituted Complex), CALM1 (Affinity Capture-MS), CALM2 (Affinity Capture-MS), CALML3 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT3 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for CAMKMT: 87 ClinVar records (4 pathogenic / likely pathogenic); 26 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	65
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (4)

Showing all 4 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4279129	GRCh37/hg19 2p21(chr2:44546016-44631587)x1	Pathogenic	criteria provided, single submitter	1
4526826	NC_000002.12:g.(?44507855)(44548633_?)del	Pathogenic	criteria provided, single submitter	1
4852100	GRCh38/hg38 2p21(chr2:44287929-44397309)x1	Pathogenic	criteria provided, single submitter	1
393873	GRCh37/hg19 2p21(chr2:44914980-45172628)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CAMKMT’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 17 predictions of 3,167):

Position(s)	Effect	Δscore	Sites
2:44362146–44362147	donor_loss	1.0000	4
2:44480070	donor_gain	1.0000
2:44754049	acceptor_gain	1.0000
2:44766562–44766563	donor_loss	1.0000	5
2:44362143	donor_gain	0.9900
2:44362146	donor_loss	0.9900
2:44373442	donor_gain	0.9900
2:44390298	donor_gain	0.9900
2:44445968	donor_gain	0.9900
2:44614542	donor_gain	0.9900

AlphaMissense

627 missense substitutions predicted likely pathogenic (of 2,114 scored), across 163 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D232	8	0.988	0.996
D178	8	0.976	0.990
F235	8	0.956	0.997
F271	8	0.925	0.990
F119	8	0.899	0.993
F225	8	0.898	0.992
H312	8	0.864	0.948
F145	8	0.846	0.950
F71	8	0.834	0.969
W212	7	0.995	0.999
W128	7	0.982	0.998
E152	7	0.975	0.986
W41	7	0.967	0.990
C233	7	0.960	0.991
D120	7	0.949	0.971
E131	7	0.929	0.988
C151	7	0.928	0.992
F68	7	0.921	0.970
N180	7	0.905	0.980
D213	7	0.879	0.959

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.000183

Disease associations

OMIM: gene MIM:609559 | disease phenotypes: MIM:220100

GenCC curated gene-disease

Mondo (1): cystinuria (MONDO:0009067)

Orphanet (1): Cystinuria (Orphanet:214)

HPO phenotypes

19 phenotypes (HPO-id order):

HPO	Term
HP:0000135	Hypogonadism
HP:0000358	Posteriorly rotated ears
HP:0000527	Long eyelashes
HP:0000787	Kidney stone
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001558	Decreased fetal movement
HP:0001611	Hypernasal speech
HP:0001943	Hypoglycemia
HP:0002007	Frontal bossing
HP:0002342	Moderate intellectual disability
HP:0002901	Hypocalcemia
HP:0003128	Lactic acidosis
HP:0003131	Cystinuria
HP:0005280	Depressed nasal bridge
HP:0200125	Mitochondrial respiratory chain defects

GWAS associations

26 associations:

Study	Trait	p-value
GCST010002_43	Refractive error	3e-26
GCST011703_43	Smoking initiation	7e-22
GCST90000047_31	Age at first sexual intercourse	1e-19
GCST002647_141	Height	2e-16
GCST007565_25	Morning person	7e-15
GCST007565_23	Morning person	1e-14
GCST003997_16	Myopia	8e-12
GCST007335_3	Age at first sexual intercourse	1e-11
GCST007325_99	General risk tolerance (MTAG)	2e-11
GCST012490_586	Femur bone mineral density x serum urate levels interaction	1e-10
GCST000817_112	Height	8e-10
GCST006941_52	Irritable mood	9e-10
GCST007576_347	Chronotype	1e-9
GCST010989_182	Body size at age 10	1e-9
GCST90000025_736	Appendicular lean mass	2e-9
GCST003369_1	Anxiety disorder (factor score)	3e-9
GCST006291_74	Spherical equivalent or myopia (age of diagnosis)	8e-9
GCST007324_99	Adventurousness	1e-8
GCST012490_149	Femur bone mineral density x serum urate levels interaction	3e-8
GCST011704_2	Smoking status (current vs never)	4e-8
GCST007325_220	General risk tolerance (MTAG)	5e-8
GCST001536_2	Immune reponse to smallpox (secreted TNF-alpha)	7e-8
GCST002179_4	Adverse response to chemotherapy in breast cancer (alopecia) (paclitaxel)	1e-6
GCST003341_12	antipsychotic drug dosage in schizophrenia or schizoaffective disorder	2e-6
GCST007102_5	Seasonality and depression	5e-6
GCST90026610_3	Bevacizumab-induced proteinuria	7e-6

EFO canonical traits (from GWAS)

16 canonical traits:

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0007792	antipsychotic drug use measurement
EFO:0007795	anxiety disorder measurement
EFO:0004847	age at onset
EFO:0009594	irritability measurement
EFO:0006876	seasonality measurement
EFO:0008579	risk-taking behaviour
EFO:0009749	age at first sexual intercourse measurement
EFO:0008328	chronotype measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0005670	smoking initiation
EFO:0006527	smoking status measurement
EFO:0004531	urate measurement
EFO:0004980	appendicular lean mass
EFO:0005943	response to bevacizumab

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D003555	Cystinuria	C12.050.351.968.419.815.885.250; C12.200.777.419.815.885.250; C12.950.419.815.885.250; C16.320.831.885.250

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	5
Benzo(a)pyrene	decreases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
testosterone enanthate	affects expression	1
beta-lapachone	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Quercetin	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

20 trials:

NCT	Phase	Status	Title
NCT02125721	Phase 4	COMPLETED	Effect of Increasing Doses of Cystine Binding Thiol Drugs on Cystine Capacity in Patients With Cystinuria
NCT02910531	Phase 2	COMPLETED	Lipoic Acid Supplement for Cystine Stone
NCT02942420	Phase 2	UNKNOWN	Bucillamine Phase 2 Trial in Patients With Cystinuria
NCT03663855	Phase 2	COMPLETED	Effect of Increasing Doses of Tiopronin on Cystine Capacity in Patients With Cystinuria
NCT04818034	Phase 2	COMPLETED	The Effect of Sodium-glucose Cotransporter (SGLT) 2 Inhibitors on Cystine Stone Formation: A Preliminary Study
NCT05058859	Phase 2	WITHDRAWN	Long Term Clinical Efficacy of Sodium-glucose Cotransporter-2 (SGLT-2) Inhibitor in Cystinurics
NCT04137978	Phase 2/3	WITHDRAWN	Study Evaluating Patients With Cystinuria
NCT04147871	Phase 2/3	WITHDRAWN	Study Evaluating Patients With Cystinuria and Efficacy and Safety Exploratory Study in the Youngest Children
NCT00381849	Phase 1/2	COMPLETED	Use of an Herbal Preparation to Prevent and Dissolve Kidney Stones
NCT00169806	Not specified	ACTIVE_NOT_RECRUITING	Randall’s Plaque Study: Pathogenesis and Relationship to Nephrolithiasis
NCT00588562	Not specified	RECRUITING	Rare Kidney Stone Consortium Patient Registry
NCT02026388	Not specified	RECRUITING	Rare Kidney Stone Consortium Biobank
NCT02120105	Not specified	COMPLETED	Cystine Capacity Clinical Study (CysCap)
NCT02124395	Not specified	COMPLETED	Health-related Quality of Life in Rare Kidney Stone
NCT02538016	Not specified	COMPLETED	TCUPS- Tolvaptan Use in Cystinuria and Urolithiasis: A Pilot Study
NCT02780297	Not specified	RECRUITING	Prospective Research Rare Kidney Stones (ProRKS)
NCT03539926	Not specified	UNKNOWN	This Study Evaluates the Superiority of Daily Self-pH Monitorization of Lit-control®pH Meter Compared to the Monitorization of Reactive Strips (Standard of Care).
NCT03836144	Not specified	COMPLETED	Effect of Urine Alkalinazation on Urinary Inflammatory Markers in Patients With Cystinuria
NCT05048563	Not specified	COMPLETED	Registry of Thiola EC Therapy
NCT06065852	Not specified	RECRUITING	National Registry of Rare Kidney Diseases