CST2

Summary

CST2 (cystatin SA, HGNC:2474) is a protein-coding gene on chromosome 20p11.21, encoding Cystatin-SA (P09228). Thiol protease inhibitor.

The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes a secreted thiol protease inhibitor found at high levels in saliva, tears and seminal plasma.

Source: NCBI Gene 1470 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 54 total
• GTEx eGene: eQTL in 11 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.95 (unconstrained)
• MANE Select transcript: NM_001322
• Notable: 54 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2474
Approved symbol	CST2
Name	cystatin SA
Location	20p11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170369
Ensembl biotype	protein_coding
OMIM	123856
Entrez	1470

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

MANE Select: ENST00000304725

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

ENST00000304725, ENST00001133499

RefSeq mRNA: 1 — MANE Select: NM_001322 NM_001322

CCDS: CCDS13161

Canonical transcript exons

ENST00000304725 — 3 exons

Exon	Start	End
ENSE00001424244	23823769	23824103
ENSE00001601194	23826433	23826729
ENSE00001625618	23825210	23825323

Expression profiles

Bgee: expression breadth ubiquitous, 116 present calls, max score 95.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 44.6392 / max 69694.6692, expressed in 167 samples.

Highest expression (Bgee): parotid gland, decidua, olfactory bulb, vena cava, adrenal tissue.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CST2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Lung	eqtl	5.3e-16	-0.52	20:23823029:A:G
Nerve Tibial	eqtl	2.5e-09	-0.33	20:23826391:A:C
Pancreas	eqtl	4.2e-07	-0.48	20:23800555:T:A
Adipose Visceral Omentum	eqtl	7.0e-07	-0.26	20:23860795:C:T
Skin Sun Exposed Lower leg	eqtl	1.4e-06	-0.31	20:23828418:A:G
Esophagus Muscularis	eqtl	1.8e-05	-0.25	20:23829044:T:C
Esophagus Gastroesophageal Junction	eqtl	3.4e-04	+1.07	20:23295907:G:A
Stomach	eqtl	7.9e-04	-0.30	20:23829044:T:C
Skin Not Sun Exposed Suprapubic	eqtl	1.5e-03	-0.23	20:23789629:C:G
Prostate	eqtl	1.6e-03	-0.39	20:23825195:G:A
Adrenal Gland	eqtl	3.2e-03	-0.45	20:23829601:C:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
186746	44.5629	166
186745	0.0481	2
186744	0.0281	2

Top tissues by expression

showing 100 of 258 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	95.98	gold quality
decidua	UBERON:0002450	89.52	gold quality
olfactory bulb	UBERON:0002264	82.15	gold quality
vena cava	UBERON:0004087	82.13	gold quality
adrenal tissue	UBERON:0018303	81.78	gold quality
pancreatic ductal cell	CL:0002079	81.77	silver quality
type B pancreatic cell	CL:0000169	81.20	gold quality
tongue	UBERON:0001723	79.86	silver quality
seminal vesicle	UBERON:0000998	79.78	gold quality
ventral tegmental area	UBERON:0002691	79.67	gold quality
pericardium	UBERON:0002407	79.32	silver quality
subthalamic nucleus	UBERON:0001906	78.80	gold quality
cardia of stomach	UBERON:0001162	78.74	gold quality
inferior vagus X ganglion	UBERON:0005363	78.60	gold quality
dorsal plus ventral thalamus	UBERON:0001897	78.53	silver quality
diaphragm	UBERON:0001103	78.31	gold quality
cerebellar vermis	UBERON:0004720	78.03	gold quality
lateral globus pallidus	UBERON:0002476	77.99	gold quality
body of tongue	UBERON:0011876	77.90	gold quality
nipple	UBERON:0002030	77.65	gold quality
pharyngeal mucosa	UBERON:0000355	77.58	silver quality
substantia nigra pars reticulata	UBERON:0001966	77.51	gold quality
lateral nuclear group of thalamus	UBERON:0002736	77.41	gold quality
substantia nigra pars compacta	UBERON:0001965	77.18	gold quality
pylorus	UBERON:0001166	77.05	gold quality
pons	UBERON:0000988	76.50	gold quality
synovial joint	UBERON:0002217	76.28	gold quality
renal medulla	UBERON:0000362	76.14	gold quality
penis	UBERON:0000989	73.77	gold quality
thymus	UBERON:0002370	73.46	silver quality
CA1 field of hippocampus	UBERON:0003881	72.57	gold quality
left ventricle myocardium	UBERON:0006566	69.18	gold quality
cardiac muscle of right atrium	UBERON:0003379	69.09	gold quality
right adrenal gland cortex	UBERON:0035827	68.20	gold quality
orbitofrontal cortex	UBERON:0004167	68.08	gold quality
gall bladder	UBERON:0002110	67.76	gold quality
right adrenal gland	UBERON:0001233	67.75	gold quality
myocardium	UBERON:0002349	67.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	67.19	gold quality
nasal cavity epithelium	UBERON:0005384	66.79	gold quality
epithelial cell of pancreas	CL:0000083	66.47	gold quality
parietal lobe	UBERON:0001872	66.44	gold quality
tongue squamous epithelium	UBERON:0006919	66.20	gold quality
triceps brachii	UBERON:0001509	65.71	gold quality
gluteal muscle	UBERON:0002000	65.62	gold quality
upper arm skin	UBERON:0004263	65.48	gold quality
mucosa of urinary bladder	UBERON:0001259	65.35	gold quality
cervix epithelium	UBERON:0004801	65.25	gold quality
adrenal cortex	UBERON:0001235	64.52	gold quality
globus pallidus	UBERON:0001875	64.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	64.12	gold quality
postcentral gyrus	UBERON:0002581	64.12	gold quality
male germ cell	CL:0000015	64.09	gold quality
gingiva	UBERON:0001828	63.45	silver quality
islet of Langerhans	UBERON:0000006	63.32	gold quality
superficial temporal artery	UBERON:0001614	62.83	gold quality
Brodmann (1909) area 46	UBERON:0006483	62.68	gold quality
adrenal gland	UBERON:0002369	62.67	gold quality
kidney epithelium	UBERON:0004819	62.38	gold quality
left adrenal gland cortex	UBERON:0035825	62.27	gold quality
sperm	CL:0000019	62.15	gold quality
cervix squamous epithelium	UBERON:0006922	62.14	gold quality
left adrenal gland	UBERON:0001234	61.97	gold quality
quadriceps femoris	UBERON:0001377	61.92	gold quality
vastus lateralis	UBERON:0001379	61.84	gold quality
entorhinal cortex	UBERON:0002728	61.49	gold quality
mammary duct	UBERON:0001765	61.30	gold quality
epithelium of mammary gland	UBERON:0003244	61.09	gold quality
deltoid	UBERON:0001476	61.04	gold quality
medial globus pallidus	UBERON:0002477	60.79	gold quality
smooth muscle tissue	UBERON:0001135	60.78	gold quality
cartilage tissue	UBERON:0002418	60.78	gold quality
tonsil	UBERON:0002372	60.58	gold quality
gingival epithelium	UBERON:0001949	60.30	gold quality
metanephric glomerulus	UBERON:0004736	60.15	gold quality
placenta	UBERON:0001987	59.98	gold quality
biceps brachii	UBERON:0001507	59.81	gold quality
mammalian vulva	UBERON:0000997	59.60	gold quality
hair follicle	UBERON:0002073	59.57	gold quality
oocyte	CL:0000023	59.53	gold quality
muscle tissue	UBERON:0002385	59.44	gold quality
nephron tubule	UBERON:0001231	59.31	gold quality
renal glomerulus	UBERON:0000074	59.25	gold quality
nasal cavity mucosa	UBERON:0001826	59.21	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	58.93	gold quality
mucosa of paranasal sinus	UBERON:0005030	58.19	silver quality
oviduct epithelium	UBERON:0004804	57.95	gold quality
skeletal muscle tissue	UBERON:0001134	57.94	gold quality
tendon of biceps brachii	UBERON:0008188	57.12	gold quality
jejunum	UBERON:0002115	56.95	gold quality
epithelium of nasopharynx	UBERON:0001951	56.72	gold quality
inferior olivary complex	UBERON:0002127	56.55	gold quality
upper leg skin	UBERON:0004262	56.53	silver quality
palpebral conjunctiva	UBERON:0001812	56.40	gold quality
amniotic fluid	UBERON:0000173	56.30	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	56.23	gold quality
prostate gland	UBERON:0002367	55.81	gold quality
corpus epididymis	UBERON:0004359	54.91	gold quality
uterine cervix	UBERON:0000002	54.82	gold quality
colonic mucosa	UBERON:0000317	54.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.96

HPA expression

RNA tissue specificity: Tissue enriched

29 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Salivary gland	tissue	5624.3	high
Pancreas	tissue	8.8	not detected
Gallbladder	tissue	4.5	not detected
Smooth muscle	tissue	3.5	not detected
Prostate	tissue	2.3	not detected
Heart muscle	tissue	2.2	not detected
Pituitary gland	tissue	1.7
Seminal vesicle	tissue	1.2	not detected
Cervix	tissue	1.0	not detected
Placenta	tissue	1.0	not detected
Thymus	tissue	0.8
Ovary	tissue	0.6	not detected
Adrenal gland	tissue	0.6	not detected
Stomach 1	tissue	0.5	not detected
Skin 1	tissue	0.3	not detected
Vagina	tissue	0.3	not detected
Adipose tissue	tissue	0.2	not detected
Lung	tissue	0.2	not detected
Fallopian tube	tissue	0.2	not detected
Pons	tissue	0.1
Parathyroid gland	tissue	0.1	not detected
Urinary bladder	tissue	0.1	not detected
Endometrium 1	tissue	0.1	not detected
Epididymis	tissue	0.1	not detected
Spleen	tissue	0.1	not detected
Liver	tissue	0.1	not detected
Small intestine	tissue	0.1	not detected
Duodenum	tissue	0.1	not detected
Locus coeruleus	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 1; highest nTPM — Blood vessel (0.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CST2 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-6753-5P	94.70	64.08	470

Functional genomics

gnomAD constraint: pLI 8.44e-15, LOEUF 1.95, missense Z -1.87 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000304725 — one region, missense o/e 1.40.

Literature-anchored findings (GeneRIF, showing 8)

• cystatins SA1 and SA2 adhere to human fibroblasts and that the event results in tyrosine phosphorylation and upregulation of the release of IL-6 mediated enhancement of NF-kappa B activity. (PMID:12413693)
• Murine monoclonal antibodies were made which can distinguish between CST1 and CST2. (PMID:15829315)
• Identification of cystatin SA as a novel inhibitor of acid ceramidase. (PMID:21846728)
• This data suggests an autoimmune mechanism behind chronic mucocutaneous candidiasis in autoimmune polyendocrine syndrome type I and provides rationale for evaluating cystatin SA1 in antifungal therapy. (PMID:23122533)
• interactions of human family 1 & 2 cystatins with cathepsin L1 (PMID:27764212)
• tumor biomarker cystatin 2 as part of a four gene transcript score has prognostic value for metastatic-lethal progression in men treated for localized prostate cancer (PMID:31376183)
• Cystatin 2 leads to a worse prognosis in patients with gastric cancer. (PMID:33302616)
• Cystatin SA attenuates gastric cancer cells growth and increases sensitivity to oxaliplatin via PI3K/AKT signaling pathway. (PMID:38717526)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:busm1-57f23.1	ENSDARG00000074425
caenorhabditis_elegans		WBGENE00000534
caenorhabditis_elegans		WBGENE00000535
caenorhabditis_elegans		WBGENE00023486

Paralogs (11): CST7 (ENSG00000077984), CST9L (ENSG00000101435), CST3 (ENSG00000101439), CST4 (ENSG00000101441), CST8 (ENSG00000125815), CSTL1 (ENSG00000125823), CST11 (ENSG00000125831), CST5 (ENSG00000170367), CST1 (ENSG00000170373), CST9 (ENSG00000173335), CST6 (ENSG00000175315)

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
Oxyuranus microlepidotus	E3P6N5	98.6%	Diamond
Pseudonaja textilis	E3P6N4	97.9%	Diamond
Oncorhynchus mykiss	Q91195	97.7%	Diamond
Oncorhynchus keta	Q98967	97.7%	Diamond
Macaca mulatta	O19092	97.3%	Diamond
Pseudechis porphyriacus	E3P6N7	97.2%	Diamond
Rattus norvegicus	Q8VIH8	96.9%	Diamond
Mus musculus	Q8VII3	96.9%	Diamond
Saimiri sciureus	O19093	94.5%	Diamond
Micropechis ikaheca	E3P6P3	93.6%	Diamond
Naja kaouthia	E3P6P4	90.9%	Diamond
Naja atra	P81714	90.9%	Diamond
Gallus gallus	P01038	90.5%	Diamond
Coturnix japonica	P81061	90.5%	Diamond
Bitis arietans	P08935	82.6%	Diamond
Bitis gabonica	Q6T6T4	82.6%	Diamond
Bos taurus	P01035	67.2%	Diamond
Oryctolagus cuniculus	O97862	66.9%	Diamond
Crotalus adamanteus	J3SE80	58.2%	Diamond
Tachypleus tridentatus	Q7M429	41.1%	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
CST5	protein-coding	1473
CST1	protein-coding	1469
GGTLC1	protein-coding	92086

Protein

Protein identifiers

Cystatin-SA — P09228 (reviewed: P09228)

Alternative names: Cystatin-2, Cystatin-S5

All UniProt accessions (1): P09228

UniProt curated annotations — full annotation on UniProt →

Function. Thiol protease inhibitor.

Subcellular location. Secreted.

Tissue specificity. Expressed in submandibular and sublingual saliva but not in parotid saliva (at protein level). Expressed in submandibular gland and parotid gland.

Similarity. Belongs to the cystatin family.

RefSeq proteins (1): NP_001313* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000010	Cystatin_dom	Domain
IPR018073	Prot_inh_cystat_CS	Conserved_site
IPR046350	Cystatin_sf	Homologous_superfamily

Pfam: PF00031

UniProt features (6 total): disulfide bond 2, signal peptide 1, chain 1, short sequence motif 1, site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09228-F1	89.89	0.74

Human Protein Atlas

Protein class: Predicted secreted proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

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

Catalytic / active sites (1)

Position	Role
32	reactive site

Disulfide bonds (2)

Type	Positions
Disulfide bond	94–104, 118–138

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: 36 (showing top): GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, VETTER_TARGETS_OF_PRKCA_AND_ETS1_DN, GOBP_DETECTION_OF_CHEMICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION_OF_TASTE, GOBP_SENSORY_PERCEPTION_OF_TASTE, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, GOMF_PEPTIDASE_REGULATOR_ACTIVITY, chr20p11, GOMF_ENZYME_INHIBITOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, GOMF_CYSTEINE_TYPE_ENDOPEPTIDASE_INHIBITOR_ACTIVITY, CHICAS_RB1_TARGETS_SENESCENT, GOBP_DETECTION_OF_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, GOBP_SENSORY_PERCEPTION_OF_BITTER_TASTE, GOMF_ENDOPEPTIDASE_REGULATOR_ACTIVITY

GO Biological Process (1): detection of chemical stimulus involved in sensory perception of bitter taste (GO:0001580)

GO Molecular Function (3): cysteine-type endopeptidase inhibitor activity (GO:0004869), protein binding (GO:0005515), peptidase inhibitor activity (GO:0030414)

GO Cellular Component (3): cytoplasm (GO:0005737), vesicle (GO:0031982), extracellular region (GO:0005576)

GO top-level categories

11 GO namespaces:

Category	Terms
cellular anatomical structure	2
detection of chemical stimulus involved in sensory perception of taste	1
sensory perception of bitter taste	1
cysteine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
binding	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
intracellular anatomical structure	1
membrane-bounded organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 8 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
detection of chemical stimulus involved in sensory perception of bitter taste	BP	direct assay

Protein interactions and networks

STRING

showing 15 of 328 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CST2	CPPED1	Q9BRF8	898
CST2	CSTA	P01040	737
CST2	CSTB	P04080	655
CST2	BST2	Q10589	605
CST2	HTN1	P15515	555
CST2	STATH	P02808	547
CST2	AZGP1	P25311	526
CST2	CTSS	P25774	440
CST2	LCN1	P31025	426
CST2	LGMN	Q99538	413
CST2	SMR3B	P02814	400
CST2	CST9	Q5W186	388
CST2	BPIFA2	Q96DR5	380
CST2	CTSB	P07858	380
CST2	C1orf198	Q9H425	370

IntAct

Human interaction partners of CST2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
ADAMTSL4	physical association	0.560	3
APPBP2	physical association	0.560	3
CYSRT1	physical association	0.560	3
KRTAP1-1	physical association	0.560	3
NOTCH2NLA	physical association	0.560	3
NOTCH2NLC	physical association	0.560	3
P4HB	physical association	0.560	3
PSMA3	physical association	0.560	3

BioGRID (72 interactions; top human partners by supporting records): GTF2B (Affinity Capture-MS; 3 records), KIR2DS2 (Affinity Capture-MS; 3 records), UCP2 (Affinity Capture-MS; 3 records), DDX31 (Affinity Capture-MS; 2 records), EPSTI1 (Affinity Capture-MS; 2 records), FRMD1 (Affinity Capture-MS; 2 records), KCNG4 (Affinity Capture-MS; 2 records), NOTCH2NL (Two-hybrid; 2 records), NPB (Affinity Capture-MS; 2 records), RCAN1 (Affinity Capture-MS; 2 records), RCAN2 (Affinity Capture-MS; 2 records), RHOBTB1 (Affinity Capture-MS; 2 records), TNFRSF19 (Affinity Capture-MS; 2 records), TSFM (Affinity Capture-MS; 2 records), ZNF491 (Affinity Capture-MS; 2 records)

Disease & clinical

Genetic variants

Variant evidence for CST2: 54 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	7
Benign	2

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 99):

Position(s)	Effect	Δscore	Sites
20:23825208–23825209	donor_loss	1.0000	3
20:23826431–23826432	donor_loss	1.0000	5
20:23826479	donor_gain	1.0000
20:23824106	acceptor_gain	0.9900
20:23825208–23825209	donor_loss	0.9900	2
20:23825325	acceptor_loss	0.9900	2
20:23825332	acceptor_gain	0.9900
20:23824104–23824105	acceptor_loss	0.9800	6
20:23825324–23825325	acceptor_loss	0.9800	3
20:23825208	donor_loss	0.9700

AlphaMissense

112 missense substitutions predicted likely pathogenic (of 917 scored), across 36 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
C94	7	0.807	0.874
C104	7	0.807	0.862
C118	7	0.797	0.908
C138	6	0.754	0.875
F120	5	0.881	0.933
F50	5	0.850	0.920
F106	5	0.849	0.906
W127	5	0.820	0.959
N56	5	0.749	0.817
F85	5	0.648	0.781
G80	5	0.619	0.681
F84	4	0.757	0.810
K96	4	0.733	0.834
T92	4	0.690	0.905
Q76	3	0.849	0.859
I122	3	0.652	0.679
Y83	3	0.618	0.662
Y55	3	0.611	0.616
E88	3	0.606	0.607
I87	2	0.718	0.783

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Prostate Adenocarcinoma)

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

4 prognostic cancer types:

Cancer	Prognostic	p-value
Colon Adenocarcinoma (validation)	unfavorable	4.84e-05
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	8.09e-05
Kidney Renal Papillary Cell Carcinoma (TCGA)	unfavorable	8.28e-05
Stomach Adenocarcinoma (TCGA)	unfavorable	0.000571

Disease associations

OMIM: gene MIM:123856 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST006585_875	Blood protein levels	1e-78

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
chlorophyllin	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
Zoledronic Acid	increases expression	1
Antimony Potassium Tartrate	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	increases expression	1
Doxorubicin	decreases expression	1
Lucanthone	increases expression	1
Silicon Dioxide	decreases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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