C1QL2

Summary

C1QL2 (complement C1q like 2, HGNC:24181) is a protein-coding gene on chromosome 2q14.2, encoding Complement C1q-like protein 2 (Q7Z5L3). May regulate the number of excitatory synapses that are formed on hippocampus neurons.

Predicted to enable identical protein binding activity. Predicted to be involved in maintenance of synapse structure and trans-synaptic signaling, modulating synaptic transmission. Predicted to be located in extracellular region. Predicted to be part of protein-containing complex. Predicted to be active in obsolete extracellular space; synapse; and synaptic cleft.

Source: NCBI Gene 165257 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 46 total — 4 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 7 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.42 (unconstrained)
• MANE Select transcript: NM_182528

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24181
Approved symbol	C1QL2
Name	complement C1q like 2
Location	2q14.2
Locus type	gene with protein product
Status	Approved
Aliases	CTRP10, C1QTNF10
Ensembl gene	ENSG00000144119
Ensembl biotype	protein_coding
OMIM	614330
Entrez	165257

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

MANE Select: ENST00000272520

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000272520, ENST00000850649, ENST00001137887

RefSeq mRNA: 1 — MANE Select: NM_182528 NM_182528

CCDS: CCDS42737

Canonical transcript exons

ENST00000272520 — 2 exons

Exon	Start	End
ENSE00000963674	119157586	119158751
ENSE00000963675	119156243	119156981

Expression profiles

Bgee: expression breadth broad, 51 present calls, max score 86.01.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4760 / max 49.5731, expressed in 133 samples.

Highest expression (Bgee): temporal lobe, amygdala, Ammon’s horn, superior frontal gyrus, anterior cingulate cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

C1QL2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 7 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

7 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	4.1e-21	+0.43	2:119160062:G:A
Brain Hippocampus	eqtl	1.4e-06	-0.25	2:119171362:C:A
Skin Not Sun Exposed Suprapubic	eqtl	7.8e-05	-0.26	2:119217204:G:A
Thyroid	eqtl	1.3e-02	+0.82	2:118346898:G:T
Brain Cerebellar Hemisphere	eqtl	1.4e-02	-0.58	2:119167246:C:T
Artery Coronary	eqtl	3.7e-02	-0.41	2:119269231:C:CA
Brain Caudate basal ganglia	eqtl	4.4e-02	+0.19	2:119170683:G:A

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
30404	0.2769	96
30408	0.0577	31
30406	0.0459	21
30407	0.0384	19
30403	0.0383	26
30405	0.0125	2
30409	0.0062	2

Top tissues by expression

showing 100 of 116 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
temporal lobe	UBERON:0001871	86.01	gold quality
amygdala	UBERON:0001876	85.99	gold quality
Ammon’s horn	UBERON:0001954	85.24	gold quality
superior frontal gyrus	UBERON:0002661	81.35	gold quality
anterior cingulate cortex	UBERON:0009835	81.34	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.54	gold quality
cerebral cortex	UBERON:0000956	79.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.63	gold quality
right frontal lobe	UBERON:0002810	79.58	gold quality
hypothalamus	UBERON:0001898	79.38	gold quality
nucleus accumbens	UBERON:0001882	78.47	gold quality
frontal cortex	UBERON:0001870	78.26	gold quality
primary visual cortex	UBERON:0002436	77.40	gold quality
prefrontal cortex	UBERON:0000451	77.09	gold quality
putamen	UBERON:0001874	74.58	gold quality
caudate nucleus	UBERON:0001873	74.44	gold quality
substantia nigra	UBERON:0002038	74.25	gold quality
brain	UBERON:0000955	72.10	gold quality
ventricular zone	UBERON:0003053	67.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	65.14	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	59.37	gold quality
ganglionic eminence	UBERON:0004023	59.02	gold quality
right hemisphere of cerebellum	UBERON:0014890	57.43	gold quality
cerebellum	UBERON:0002037	56.87	gold quality
cerebellar cortex	UBERON:0002129	56.73	gold quality
cerebellar hemisphere	UBERON:0002245	56.61	gold quality
skin of leg	UBERON:0001511	46.00	gold quality
zone of skin	UBERON:0000014	43.48	gold quality
adenohypophysis	UBERON:0002196	42.45	gold quality
lymph node	UBERON:0000029	41.87	silver quality
skin of abdomen	UBERON:0001416	40.23	gold quality
cortical plate	UBERON:0005343	39.94	gold quality
bone marrow cell	CL:0002092	39.89	gold quality
pituitary gland	UBERON:0000007	39.08	gold quality
mucosa of stomach	UBERON:0001199	38.63	silver quality
lower esophagus mucosa	UBERON:0035834	37.45	gold quality
apex of heart	UBERON:0002098	37.40	silver quality
anatomical system	UBERON:0000467	37.25	gold quality
multicellular organism	UBERON:0000468	37.25	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
heart left ventricle	UBERON:0002084	37.17	gold quality
cortex of kidney	UBERON:0001225	36.53	gold quality
thoracic mammary gland	UBERON:0005200	35.85	gold quality
corpus callosum	UBERON:0002336	35.51	gold quality
bone marrow	UBERON:0002371	33.65	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
right lobe of liver	UBERON:0001114	33.32	silver quality
tonsil	UBERON:0002372	33.12	gold quality
heart	UBERON:0000948	32.66	silver quality
muscle tissue	UBERON:0002385	32.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
left ovary	UBERON:0002119	32.10	silver quality
muscle of leg	UBERON:0001383	31.89	gold quality
gastrocnemius	UBERON:0001388	31.87	gold quality
body of pancreas	UBERON:0001150	31.84	gold quality
pancreas	UBERON:0001264	31.56	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
tibial artery	UBERON:0007610	30.47	gold quality
popliteal artery	UBERON:0002250	30.46	gold quality
blood	UBERON:0000178	30.40	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
islet of Langerhans	UBERON:0000006	29.67	gold quality
placenta	UBERON:0001987	29.18	gold quality
monocyte	CL:0000576	29.12	gold quality
leukocyte	CL:0000738	28.98	gold quality
tibial nerve	UBERON:0001323	28.98	gold quality
right uterine tube	UBERON:0001302	28.74	gold quality
saliva-secreting gland	UBERON:0001044	28.39	gold quality
kidney	UBERON:0002113	28.31	gold quality
right lobe of thyroid gland	UBERON:0001119	28.30	gold quality
thoracic aorta	UBERON:0001515	28.16	gold quality
duodenum	UBERON:0002114	28.14	gold quality
left lobe of thyroid gland	UBERON:0001120	28.10	gold quality
ascending aorta	UBERON:0001496	28.05	gold quality
smooth muscle tissue	UBERON:0001135	27.50	gold quality
minor salivary gland	UBERON:0001830	27.40	gold quality
right atrium auricular region	UBERON:0006631	27.21	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	27.00	gold quality
uterine cervix	UBERON:0000002	26.82	gold quality
descending thoracic aorta	UBERON:0002345	26.68	gold quality
right coronary artery	UBERON:0001625	26.58	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
left adrenal gland cortex	UBERON:0035825	26.13	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
right testis	UBERON:0004534	25.82	gold quality
adipose tissue	UBERON:0001013	25.36	silver quality
body of stomach	UBERON:0001161	25.36	gold quality
myometrium	UBERON:0001296	25.29	gold quality
omental fat pad	UBERON:0010414	25.01	silver quality
ectocervix	UBERON:0012249	24.95	gold quality
muscle layer of sigmoid colon	UBERON:0035805	24.89	gold quality
prostate gland	UBERON:0002367	24.86	gold quality
right adrenal gland cortex	UBERON:0035827	24.77	gold quality
right lung	UBERON:0002167	24.76	gold quality
left adrenal gland	UBERON:0001234	24.46	gold quality
adult mammalian kidney	UBERON:0000082	24.33	gold quality
metanephros cortex	UBERON:0010533	24.06	gold quality
colon	UBERON:0001155	24.03	gold quality
esophagus mucosa	UBERON:0002469	24.02	gold quality
endometrium	UBERON:0001295	23.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-137537	yes	5.64
E-ANND-3	no	0.98

HPA expression

RNA tissue specificity: Tissue enriched

38 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Hippocampus	tissue	32.5
Cerebral cortex	tissue	20.0
Motor cortex	tissue	20.0
Amygdala	tissue	14.1
Substantia nigra	tissue	14.0
Hippocampal formation	tissue	10.3
Retrosplenial and cingulate cortex	tissue	9.9
Prefrontal cortex	tissue	9.7
Retrosplenial cortex	tissue	9.7
Hypothalamus	tissue	9.0
Postcentral gyrus	tissue	8.1
Nucleus accumbens	tissue	7.6
Periaqueductal gray	tissue	7.5
Insular cortex	tissue	7.5
Temporal cortex	tissue	5.1
Locus coeruleus	tissue	4.7
Septum	tissue	4.6
Somatosensory cortex	tissue	4.2
Pons	tissue	3.8
Midbrain	tissue	3.5
Corpus callosum	tissue	3.5
Ventral forebrain	tissue	3.5
Medulla oblongata	tissue	3.2
Retina	tissue	2.7
Entorhinal cortex	tissue	2.7
Occipital cortex	tissue	2.5
Thalamus	tissue	2.4
Superior colliculi	tissue	2.1
Spinal cord	tissue	1.9
Olfactory bulb	tissue	1.7
Putamen	tissue	1.3
Basal ganglia	tissue	1.1
Caudate putamen	tissue	1.0
Frontal cortex	tissue	0.9
Pituitary gland	tissue	0.5
Choroid plexus	tissue	0.5
Cerebellum	tissue	0.4
Lymph node	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Hippocampus, CA3 (48.7), Hippocampus, CA1 (41.4), Ventromedial nucleus (35.8), Dentate gyrus (30.8), Corticomedial amygdala (30.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting C1QL2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

10 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-214-5P	97.34	66.50	617
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-5702	96.68	68.21	958
HSA-MIR-3677-5P	93.16	64.62	393

Functional genomics

gnomAD constraint: pLI 6.22e-05, LOEUF 1.42, missense Z -0.458 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000272520 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
2:119,156,805–119,156,975	43 / 74.8	0.57	no
2:119,156,976–119,158,269	353 / 334.8	1.05	no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	c1ql2	ENSDARG00000015592
mus_musculus	C1ql2	ENSMUSG00000036907
rattus_norvegicus	C1ql2	ENSRNOG00000046863

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QL1 (ENSG00000131094), C1QTNF6 (ENSG00000133466), COL8A1 (ENSG00000144810), C1QTNF2 (ENSG00000145861), C1QC (ENSG00000159189), C1QTNF7 (ENSG00000163145), C1QL3 (ENSG00000165985), COL8A2 (ENSG00000171812), C1QTNF4 (ENSG00000172247), C1QB (ENSG00000173369), C1QA (ENSG00000173372), C1QTNF1 (ENSG00000173918), ADIPOQ (ENSG00000181092), OTOL1 (ENSG00000182447), C1QTNF8 (ENSG00000184471), C1QL4 (ENSG00000186897), C1QTNF9B (ENSG00000205863), C1QTNF5 (ENSG00000223953), C1QTNF9 (ENSG00000240654)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:3032521) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 10 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal spleen morphology	1
impaired coordination	1
impaired balance	1
female infertility	1
abnormal motor capabilities/coordination/movement	1
abnormal kidney morphology	1
enlarged kidney	1
abnormal mitochondrial ATP synthesis coupled electron transport	1
abnormal oxidative phosphorylation	1
impaired fine motor coordination	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
Bos taurus	P86437	100.0%	Diamond
Oryctolagus cuniculus	P14282	99.7%	Diamond
Gallus gallus	Q7LZR2	99.7%	Diamond
Oncorhynchus mykiss	A0A060WQA3	89.4%	Diamond
Oncorhynchus keta	P83371	89.4%	Diamond
Lepomis macrochirus	P98085	81.3%	Diamond
Sus scrofa	Q69DL0	78.5%	Diamond
Tamias sibiricus	Q06576	57.9%	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
STEAP3-AS1	ncRNA	100874111
STEAP3	protein-coding	55240
MARCO	protein-coding	8685
LINC01956	ncRNA	124905956
EN1	protein-coding	2019

Protein

Protein identifiers

Complement C1q-like protein 2 — Q7Z5L3 (reviewed: Q7Z5L3)

Alternative names: C1q and tumor necrosis factor-related protein 10

All UniProt accessions (2): A0A3B0IND4, Q7Z5L3

UniProt curated annotations — full annotation on UniProt →

Function. May regulate the number of excitatory synapses that are formed on hippocampus neurons. Has no effect on inhibitory synapses.

Subunit / interactions. Forms homotrimers which can further assemble to form higher-order oligomeric complexes. Interacts with ADGRB3. May interact with ERFE. Forms heterooligomers with C1QL3 and C1QL4, when proteins are coexpressed; this interaction does not occur after secretion.

Subcellular location. Secreted.

RefSeq proteins (1): NP_872334* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001073	C1q_dom	Domain
IPR008160	Collagen	Repeat
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR050822	Cerebellin_Synaptic_Org	Family

Pfam: PF00386, PF01391

UniProt features (8 total): domain 2, sequence conflict 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z5L3-F1	75.90	0.45

Human Protein Atlas

Protein class: Transporters, Accessory Factors Involved in Transport, Predicted secreted proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; cytosol

Antibody reliability (HPA): IH uncertain · IF approved

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 71 (showing top): PAX4_01, GOBP_SYNAPSE_ASSEMBLY, GOCC_COLLAGEN_TRIMER, GOBP_CELLULAR_COMPONENT_MAINTENANCE, AP2_Q3, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, AAAGACA_MIR511, GOBP_ORGANELLE_ASSEMBLY, GOBP_SYNAPTIC_SIGNALING, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_CELL_JUNCTION_ASSEMBLY, GOBP_PROTEIN_LOCALIZATION_TO_SYNAPSE

GO Biological Process (5): regulation of synapse maturation (GO:0090128), postsynaptic density assembly (GO:0097107), trans-synaptic signaling, modulating synaptic transmission (GO:0099550), maintenance of synapse structure (GO:0099558), neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0099645)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (7): protein-containing complex (GO:0032991), synaptic cleft (GO:0043083), synapse (GO:0045202), hippocampal mossy fiber to CA3 synapse (GO:0098686), cerebellar climbing fiber to Purkinje cell synapse (GO:0150053), extracellular region (GO:0005576), glutamatergic synapse (GO:0098978)

GO top-level categories

26 GO namespaces:

Category	Terms
cellular anatomical structure	2
regulation of developmental process	1
regulation of synapse organization	1
synapse maturation	1
postsynaptic density organization	1
postsynaptic specialization assembly	1
excitatory synapse assembly	1
chemical synaptic transmission	1
modulation of chemical synaptic transmission	1
trans-synaptic signaling	1
cell junction maintenance	1
synapse organization	1
protein-containing complex localization	1
receptor localization to synapse	1
regulation of postsynaptic membrane neurotransmitter receptor levels	1
protein localization to postsynaptic specialization membrane	1
protein binding	1
binding	1
cellular_component	1
extracellular region	1
cell junction	1
thorny excrescence	1
neuron to neuron synapse	1
hippocampal mossy fiber expansion	1
asymmetric, glutamatergic, excitatory synapse	1
synapse	1

Protein interactions and networks

STRING

showing 15 of 800 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
C1QL2	BEND5	Q7L4P6	530
C1QL2	ADGRB3	O60242	514
C1QL2	DPY19L4	Q7Z388	468
C1QL2	TMEM9B	Q9NQ34	441
C1QL2	CCNQ	Q8N1B3	440
C1QL2	FIBCD1	Q8N539	434
C1QL2	SLC45A1	Q9Y2W3	431
C1QL2	KCTD20	Q7Z5Y7	425
C1QL2	HABP4	Q5JVS0	422
C1QL2	SPOCK1	Q08629	407
C1QL2	NRXN2	Q9P2S2	406
C1QL2	KCNH4	Q9UQ05	404
C1QL2	NXPH4	O95158	400
C1QL2	MPPED1	O15442	399
C1QL2	NRXN1	Q9ULB1	399

IntAct

BioGRID (1 interactions; top human partners by supporting records): BAI3 (Affinity Capture-MS)

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
ADGRB3	ligand	Signaling by Complement

Disease & clinical

Genetic variants

Variant evidence for C1QL2: 46 ClinVar records (5 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	38
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (5)

Showing all 5 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
1809385	GRCh37/hg19 2q14.1-14.3(chr2:116761476-123897262)x1	Pathogenic	criteria provided, single submitter	1
4755368	GRCh38/hg38 2q14.1-14.3(chr2:115987911-123142972)x1	Pathogenic	criteria provided, single submitter	1
3062627	GRCh37/hg19 2q14.1-14.3(chr2:116646793-126388760)x1	Likely pathogenic	criteria provided, single submitter	1
155658	GRCh38/hg38 2q14.2-14.3(chr2:118687829-121621814)x1	Pathogenic	no assertion criteria provided	1
442443	GRCh37/hg19 2q14.1-14.3(chr2:116754600-123897370)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore C1QL2’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; 18 predictions of 195):

Position(s)	Effect	Δscore	Sites
2:119156982–119156983	acceptor_loss	1.0000	5
2:119156982	acceptor_loss	0.9900
2:119157584–119157585	donor_loss	0.9900	5
2:119157588	donor_gain	0.9900
2:119157411	donor_gain	0.9400
2:119156990	acceptor_gain	0.9200
2:119157584	donor_loss	0.9100
2:119157121	donor_gain	0.8800
2:119157130	donor_gain	0.8700
2:119156994	acceptor_gain	0.8600

AlphaMissense

997 missense substitutions predicted likely pathogenic (of 1,856 scored), across 183 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
M211	9	0.990	1.000
M219	9	0.977	1.000
M31	9	0.900	0.988
M25	9	0.872	0.980
D237	8	0.999	1.000
D243	8	0.999	1.000
D222	8	0.998	1.000
D264	8	0.998	1.000
F205	8	0.997	1.000
D215	8	0.997	1.000
F279	8	0.997	1.000
F161	8	0.996	1.000
D239	8	0.996	1.000
H269	8	0.996	1.000
S218	8	0.995	1.000
S232	8	0.995	1.000
D257	8	0.995	1.000
N274	8	0.994	1.000
F177	8	0.992	1.000
D179	8	0.989	0.998

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Lung Adenocarcinoma)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (TCGA)	favorable	0.000944

Disease associations

OMIM: gene MIM:614330 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST009391_236	Metabolite levels	7e-6
GCST002688_3	Very long-chain saturated fatty acid levels (fatty acid 22:0)	8e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0010424	triacylglycerol 54:6 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Copper	affects cotreatment, decreases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Malathion	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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