ASPRV1

Summary

ASPRV1 (aspartic peptidase retroviral like 1, HGNC:26321) is a protein-coding gene on chromosome 2p13.3, encoding Retroviral-like aspartic protease 1 (Q53RT3). Protease responsible for filaggrin processing, essential for the maintenance of a proper epidermis organization.

Filaggrin is a structural protein that is crucial for in the development and maintenance of the skin barrier. This gene encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. Expression is found primarily in the epidermis and inner root sheath of hair follicles.

Source: NCBI Gene 151516 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ichthyosis, lamellar, autosomal dominant (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 90 total — 3 pathogenic
• Phenotypes (HPO): 44
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.25 (unconstrained)
• MANE Select transcript: NM_152792

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26321
Approved symbol	ASPRV1
Name	aspartic peptidase retroviral like 1
Location	2p13.3
Locus type	gene with protein product
Status	Approved
Aliases	Taps, SASPase, FLJ25084
Ensembl gene	ENSG00000244617
Ensembl biotype	protein_coding
OMIM	611765
Entrez	151516

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

MANE Select: ENST00000320256

ENST00000320256

RefSeq mRNA: 1 — MANE Select: NM_152792 NM_152792

CCDS: CCDS1897

Canonical transcript exons

ENST00000320256 — 1 exons

Exon	Start	End
ENSE00001221518	69960089	69961631

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 99.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4188 / max 359.6161, expressed in 35 samples.

Highest expression (Bgee): upper arm skin, upper leg skin, nipple, penis, skin of leg.

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
28956	0.4188	35

Top tissues by expression

showing 100 of 233 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	99.82	gold quality
upper leg skin	UBERON:0004262	99.56	gold quality
nipple	UBERON:0002030	98.64	gold quality
penis	UBERON:0000989	97.99	gold quality
skin of leg	UBERON:0001511	97.99	gold quality
skin of hip	UBERON:0001554	97.99	gold quality
mammalian vulva	UBERON:0000997	97.83	gold quality
zone of skin	UBERON:0000014	97.63	gold quality
skin of abdomen	UBERON:0001416	96.96	gold quality
pancreatic ductal cell	CL:0002079	88.09	silver quality
endothelial cell	CL:0000115	86.87	gold quality
blood	UBERON:0000178	81.48	gold quality
tibialis anterior	UBERON:0001385	80.26	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.63	gold quality
amniotic fluid	UBERON:0000173	79.58	gold quality
ileal mucosa	UBERON:0000331	75.76	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	75.64	gold quality
spinal cord	UBERON:0002240	74.54	gold quality
hypothalamus	UBERON:0001898	72.37	gold quality
cerebellar hemisphere	UBERON:0002245	72.20	gold quality
right hemisphere of cerebellum	UBERON:0014890	72.08	gold quality
cerebellar cortex	UBERON:0002129	72.04	gold quality
deltoid	UBERON:0001476	72.02	silver quality
putamen	UBERON:0001874	72.00	gold quality
cerebellum	UBERON:0002037	71.68	gold quality
left ovary	UBERON:0002119	71.50	gold quality
substantia nigra	UBERON:0002038	71.23	gold quality
tibia	UBERON:0000979	71.04	gold quality
cortical plate	UBERON:0005343	70.89	gold quality
right frontal lobe	UBERON:0002810	70.87	gold quality
ganglionic eminence	UBERON:0004023	70.86	gold quality
amygdala	UBERON:0001876	70.81	gold quality
anterior cingulate cortex	UBERON:0009835	70.78	gold quality
ventricular zone	UBERON:0003053	70.72	gold quality
nucleus accumbens	UBERON:0001882	70.65	gold quality
gingiva	UBERON:0001828	70.36	gold quality
caudate nucleus	UBERON:0001873	70.33	gold quality
right ovary	UBERON:0002118	70.30	gold quality
midbrain	UBERON:0001891	70.24	gold quality
gastrocnemius	UBERON:0001388	70.19	gold quality
muscle of leg	UBERON:0001383	70.00	gold quality
prefrontal cortex	UBERON:0000451	69.34	gold quality
ovary	UBERON:0000992	69.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	69.22	gold quality
tibial nerve	UBERON:0001323	68.98	gold quality
brain	UBERON:0000955	68.96	gold quality
neocortex	UBERON:0001950	68.78	gold quality
gingival epithelium	UBERON:0001949	68.70	gold quality
forebrain	UBERON:0001890	68.69	gold quality
pituitary gland	UBERON:0000007	68.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.63	gold quality
subcutaneous adipose tissue	UBERON:0002190	68.63	gold quality
Ammon’s horn	UBERON:0001954	68.54	gold quality
adenohypophysis	UBERON:0002196	68.50	gold quality
quadriceps femoris	UBERON:0001377	68.48	gold quality
body of uterus	UBERON:0009853	68.46	gold quality
frontal cortex	UBERON:0001870	68.26	gold quality
right adrenal gland cortex	UBERON:0035827	68.16	gold quality
anatomical system	UBERON:0000467	67.99	gold quality
cerebral cortex	UBERON:0000956	67.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	67.99	gold quality
multicellular organism	UBERON:0000468	67.86	gold quality
material anatomical entity	UBERON:0000465	67.85	gold quality
apex of heart	UBERON:0002098	67.72	gold quality
primary visual cortex	UBERON:0002436	67.70	gold quality
mucosa of stomach	UBERON:0001199	67.66	gold quality
right lung	UBERON:0002167	67.64	gold quality
left adrenal gland cortex	UBERON:0035825	67.49	gold quality
spleen	UBERON:0002106	67.43	gold quality
granulocyte	CL:0000094	67.28	gold quality
adrenal cortex	UBERON:0001235	67.24	gold quality
ectocervix	UBERON:0012249	67.20	gold quality
layer of synovial tissue	UBERON:0007616	67.16	silver quality
hindlimb stylopod muscle	UBERON:0004252	67.14	gold quality
skeletal muscle tissue	UBERON:0001134	67.00	gold quality
left adrenal gland	UBERON:0001234	66.98	gold quality
vastus lateralis	UBERON:0001379	66.97	gold quality
left uterine tube	UBERON:0001303	66.95	gold quality
endocervix	UBERON:0000458	66.94	gold quality
temporal lobe	UBERON:0001871	66.88	gold quality
cardiac muscle of right atrium	UBERON:0003379	66.71	gold quality
right adrenal gland	UBERON:0001233	66.57	gold quality
muscle tissue	UBERON:0002385	66.55	gold quality
middle temporal gyrus	UBERON:0002771	66.51	silver quality
adipose tissue	UBERON:0001013	66.46	gold quality
occipital lobe	UBERON:0002021	66.26	gold quality
left ventricle myocardium	UBERON:0006566	66.25	gold quality
Brodmann (1909) area 23	UBERON:0013554	66.05	silver quality
adipose tissue of abdominal region	UBERON:0007808	66.00	gold quality
lower esophagus muscularis layer	UBERON:0035833	66.00	gold quality
omental fat pad	UBERON:0010414	65.95	gold quality
lower esophagus	UBERON:0013473	65.95	gold quality
peritoneum	UBERON:0002358	65.94	gold quality
popliteal artery	UBERON:0002250	65.89	gold quality
tibial artery	UBERON:0007610	65.89	gold quality
myocardium	UBERON:0002349	65.76	gold quality
aorta	UBERON:0000947	65.58	gold quality
myometrium	UBERON:0001296	65.54	gold quality
right coronary artery	UBERON:0001625	65.40	gold quality
uterine cervix	UBERON:0000002	65.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.85

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skin 1	tissue	343.5	high
Breast	tissue	23.5	not detected
Nucleus accumbens	tissue	7.7
Locus coeruleus	tissue	6.6
Hippocampus	tissue	5.7	not detected
Postcentral gyrus	tissue	5.6
Skeletal muscle	tissue	4.9	not detected
Ovary	tissue	3.2	not detected
Epididymis	tissue	3.0	not detected
Pituitary gland	tissue	2.9
Vagina	tissue	2.9	not detected
Thymus	tissue	2.4
Tongue	tissue	2.3
Testis	tissue	2.1	not detected
Choroid plexus	tissue	2.1
Spleen	tissue	1.8	not detected
Duodenum	tissue	1.8	not detected
Fallopian tube	tissue	1.8	not detected
Endometrium 1	tissue	1.6	not detected
Cervix	tissue	1.5	medium
Retina	tissue	1.5
Small intestine	tissue	1.5	not detected
Seminal vesicle	tissue	1.4	not detected
Kidney	tissue	1.4	medium
Corpus callosum	tissue	1.4
Adrenal gland	tissue	1.4	not detected
Adipose tissue	tissue	1.3	not detected
Gallbladder	tissue	1.2	not detected
Smooth muscle	tissue	1.1	not detected
Lymph node	tissue	1.0	not detected
Placenta	tissue	1.0	high
Bone marrow	tissue	1.0	not detected
Tonsil	tissue	1.0	not detected
Periaqueductal gray	tissue	1.0
Appendix	tissue	1.0	not detected
Stomach 1	tissue	0.9	not detected
Heart muscle	tissue	0.9	not detected
Frontal cortex	tissue	0.9
Lung	tissue	0.9	not detected
Cerebral cortex	tissue	0.8	not detected
Esophagus	tissue	0.8	not detected
Salivary gland	tissue	0.8	not detected
Basal ganglia	tissue	0.8	not detected
Amygdala	tissue	0.8
Cerebellum	tissue	0.8	not detected
Spinal cord	tissue	0.8
Ventral forebrain	tissue	0.8
Insular cortex	tissue	0.8
Hypothalamus	tissue	0.7
Prostate	tissue	0.7	not detected
Hippocampal formation	tissue	0.7
Entorhinal cortex	tissue	0.7
Olfactory bulb	tissue	0.7
Septum	tissue	0.7
Colon	tissue	0.6	not detected
Putamen	tissue	0.6
Midbrain	tissue	0.6
Substantia nigra	tissue	0.6
Liver	tissue	0.6	not detected
Temporal cortex	tissue	0.6

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Parieto-temporal junction (white matter) (16.9), Temporal white matter (14.1), Corpus callosum, genu (white matter) (12.8), Angular gyrus (white matter) (12.5), Nucleus ambiguus (12.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting ASPRV1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 37 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-655-5P	98.74	65.93	888
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-1271-3P	97.56	64.85	865
HSA-MIR-550A-3-5P	97.56	65.35	823
HSA-MIR-550A-5P	97.56	65.35	823

Functional genomics

gnomAD constraint: pLI 0.00174, LOEUF 1.25, missense Z 0.78 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000320256 — one region, missense o/e 0.93.

Literature-anchored findings (GeneRIF, showing 7)

• Identification and characterization of a new member of the aspartic proteases family, a unique epidermal retroviral-like protease, Skin ASpartic Protease. (PMID:16098038)
• Taps expression is negatively associated with dedifferentiation and malignant progression in squamous cell carcinomas of the skin. (PMID:16565508)
• SASPase activity is indispensable for processing profilaggrin and maintaining the texture and hydration of the stratum corneum. (PMID:21542132)
• results failed to find an association between ASPRV1 gene mutations and atopic eczema or clinically dry skin in the European populations studied (PMID:22318384)
• Filaggrin and filaggrin 2 processing are linked together through skin aspartic acid protease activation. (PMID:32437351)
• Mutations in ASPRV1 Cause Dominantly Inherited Ichthyosis. (PMID:32516568)
• Biochemical Characterization of Human Retroviral-Like Aspartic Protease 1 (ASPRV1). (PMID:32640672)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Asprv1	ENSMUSG00000033508
rattus_norvegicus	Asprv1	ENSRNOG00000017710

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915105) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
wrinkled skin	1
abnormal coat appearance	1

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
PCBP1-AS1	ncRNA	400960
MXD1	protein-coding	4084
PCBP1	protein-coding	5093
ANXA4	protein-coding	307
GMCL1	protein-coding	64395
SNRNP27	protein-coding	11017
LINC01816	ncRNA	100133985

Protein

Protein identifiers

Retroviral-like aspartic protease 1 — Q53RT3 (reviewed: Q53RT3)

Alternative names: Skin-specific retroviral-like aspartic protease, TPA-inducible aspartic proteinase-like protein

All UniProt accessions (1): Q53RT3

UniProt curated annotations — full annotation on UniProt →

Function. Protease responsible for filaggrin processing, essential for the maintenance of a proper epidermis organization.

Subunit / interactions. Homodimer.

Subcellular location. Membrane.

Tissue specificity. Expressed primarily in the granular layer of the epidermis and inner root sheath of hair follicles. In psoriatic skin, expressed throughout the stratum corneum. In ulcerated skin, expressed in the stratum granulosum of intact epidermis but almost absent from ulcerated regions. Expressed in differentiated areas of squamous cell carcinomas but not in undifferentiated tumors.

Post-translational modifications. Undergoes autocleavage which is necessary for activation of the protein.

Disease relevance. Ichthyosis, lamellar, autosomal dominant (ADLI) [MIM:146750] An autosomal dominant form of ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling. ADLI is characterized by onset at birth or within the first months of life, skin scaling on the entire body with relative sparing of face, anterior chest, and abdomen, and palmoplantar keratoderma. Patients may manifest mild erythema and moderate pruritus. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q53RT3-1	1	yes
Q53RT3-2	2

RefSeq proteins (1): NP_690005* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001969	Aspartic_peptidase_AS	Active_site
IPR001995	Peptidase_A2_cat	Domain
IPR021109	Peptidase_aspartic_dom_sf	Homologous_superfamily
IPR033539	Asprv1	Family

Pfam: PF13975

UniProt features (16 total): sequence variant 4, propeptide 2, topological domain 2, chain 1, mutagenesis site 1, sequence conflict 1, transmembrane region 1, domain 1, active site 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures by resolution:

PDB	Title	Method	Resolution (Å)
27JK	Crystal structure of the mature form of human ASPRV1 (K199E, form 1)	X-RAY DIFFRACTION	1.84
27IV	Crystal structure of the mature form of human ASPRV1 bound to self-cleavage peptide	X-RAY DIFFRACTION	1.95
27JQ	Crystal structure of the mature form of human ASPRV1-14(R311P)	X-RAY DIFFRACTION	1.95
27JO	Crystal structure of the mature form of human ASPRV1 bound to indinavir	X-RAY DIFFRACTION	2.08
27IQ	Crystal structure of the mature form of human ASPRV1 bound to filaggrin peptide	X-RAY DIFFRACTION	2.09
27JP	Crystal structure of the mature form of human ASPRV1	X-RAY DIFFRACTION	2.35
27IK	Crystal structure of the mature form of human ASPRV1	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53RT3-F1	70.77	0.44

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of skin

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH enhanced · IF approved

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
212

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	276

Mutagenesis-validated functional residues (1)

Position	Phenotype
212	abolishes production of active form of enzyme.

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: 115 (showing top): GOBP_PROTEIN_MATURATION, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, GOBP_SKIN_DEVELOPMENT, RICKMAN_HEAD_AND_NECK_CANCER_C, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, GOMF_ASPARTIC_TYPE_PEPTIDASE_ACTIVITY, chr2p13, MIKKELSEN_ES_ICP_WITH_H3K4ME3, CHYLA_CBFA2T3_TARGETS_DN, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, GOBP_PROTEIN_PROCESSING, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GSE13522_CTRL_VS_T_CRUZI_BRAZIL_STRAIN_INF_SKIN_DN, GSE11924_TH2_VS_TH17_CD4_TCELL_UP

GO Biological Process (3): protein processing (GO:0016485), skin development (GO:0043588), proteolysis (GO:0006508)

GO Molecular Function (3): aspartic-type endopeptidase activity (GO:0004190), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

10 GO namespaces:

Category	Terms
proteolysis	1
protein maturation	1
animal organ development	1
protein metabolic process	1
endopeptidase activity	1
aspartic-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 7 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
protein processing	BP	direct assay
aspartic-type endopeptidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 396 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASPRV1	PNMA8C	A0A1B0GUJ8	597
ASPRV1	PNPLA1	Q8N8W4	581
ASPRV1	NIPAL4	Q0D2K0	575
ASPRV1	CASP14	P31944	551
ASPRV1	PNMA8A	Q86V59	537
ASPRV1	TGM1	P22735	536
ASPRV1	SLC27A4	Q6P1M0	499
ASPRV1	BLMH	Q13867	498
ASPRV1	RTL6	Q6ICC9	479
ASPRV1	ERVMER34-1	Q9H9K5	461
ASPRV1	KRT27	Q7Z3Y8	455
ASPRV1	KRT10	P13645	441
ASPRV1	FAM25A	B3EWG3	418
ASPRV1	ABHD5	Q8WTS1	405
ASPRV1	RTL5	Q5HYW3	403

IntAct

Human interaction partners of ASPRV1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
WDR45B	association	0.530	2
ELMOD3	physical association	0.400	1
SLC25A6	physical association	0.400	1
CDKN2A	physical association	0.370	1

BioGRID (37 interactions; top human partners by supporting records): ELMOD3 (Affinity Capture-MS; 2 records), FCF1 (Affinity Capture-MS; 2 records), GNB1L (Affinity Capture-MS; 2 records), MCL1 (Affinity Capture-MS; 2 records), RAB9B (Affinity Capture-MS; 2 records), WDR45B (Affinity Capture-MS; 2 records), B3GALNT1 (Affinity Capture-MS), C21orf59 (Affinity Capture-MS), CCR1 (Affinity Capture-MS), CDKN2A (Two-hybrid), CUL2 (Affinity Capture-MS), DDX39B (Affinity Capture-MS), ESR2 (Affinity Capture-MS), FIS1 (Affinity Capture-MS), FNDC5 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for ASPRV1: 90 ClinVar records (3 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	65
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (3)

Showing all 3 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
977277	NM_152792.4(ASPRV1):c.343A>G (p.Lys115Glu)	Pathogenic	no assertion criteria provided	1
977278	NM_152792.4(ASPRV1):c.688C>A (p.Pro230Thr)	Pathogenic	no assertion criteria provided	1
977279	NM_152792.4(ASPRV1):c.680G>C (p.Arg227Pro)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ASPRV1’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; 11 predictions of 62):

Position(s)	Effect	Δscore	Sites
2:69960619	donor_gain	0.9500
2:69960668	donor_gain	0.9000
2:69960660	donor_gain	0.8900
2:69960768	donor_gain	0.8900
2:69960727	donor_gain	0.8200
2:69960633	donor_gain	0.7800
2:69961286	donor_gain	0.6400
2:69960618–69960620	donor_gain	0.5700	2
2:69960621	donor_gain	0.5100
2:69960670	donor_gain	0.5100

AlphaMissense

695 missense substitutions predicted likely pathogenic (of 2,241 scored), across 165 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
D212	8	0.995	0.998
F272	8	0.976	0.999
F298	8	0.964	0.995
D287	8	0.962	0.990
F209	8	0.961	0.998
F310	8	0.948	0.998
D297	8	0.945	0.985
F239	8	0.911	0.991
F188	8	0.907	0.971
W225	7	0.991	0.998
W257	7	0.988	0.998
C303	7	0.979	0.998
M251	7	0.957	0.995
F323	7	0.938	0.990
F106	7	0.927	0.974
W129	7	0.925	0.978
W116	7	0.900	0.960
I253	7	0.879	0.995
H221	7	0.834	0.950
D324	7	0.771	0.802

HPA cancer prognostics

RNA cancer specificity: Group enriched (Head and Neck Squamous Cell Carcinoma, Skin Cutaneous Melanoma)

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000231

Disease associations

OMIM: gene MIM:611765 | disease phenotypes: MIM:146750

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
ichthyosis, lamellar, autosomal dominant	Strong	Autosomal dominant	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

1 panels:

Panel	Rating
Ichthyosis and erythrokeratoderma	green

Mondo (1): ichthyosis, lamellar, autosomal dominant (MONDO:0007812)

HPO phenotypes

44 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000405	Conductive hearing impairment
HP:0000491	Keratitis
HP:0000498	Blepharitis
HP:0000518	Cataract
HP:0000563	Keratoconus
HP:0000621	Entropion
HP:0000656	Ectropion
HP:0000958	Dry skin
HP:0000962	Hyperkeratosis
HP:0000966	Hypohidrosis
HP:0000982	Palmoplantar keratoderma
HP:0000989	Pruritus
HP:0001019	Erythroderma
HP:0001596	Alopecia
HP:0001944	Dehydration
HP:0002046	Heat intolerance
HP:0002719	Recurrent infections
HP:0003121	Limb joint contracture
HP:0004552	Scarring alopecia of scalp
HP:0007479	Congenital nonbullous ichthyosiform erythroderma
HP:0007717	Chronic irritative conjunctivitis
HP:0008064	Ichthyosis
HP:0008070	Sparse hair
HP:0008404	Nail dystrophy
HP:0009775	Amniotic constriction ring
HP:0011039	Abnormal helix morphology
HP:0011457	Loss of eyelashes
HP:0012472	Eclabion
HP:0012531	Pain
HP:0012804	Corneal ulceration
HP:0012905	Euryblepharon
HP:0025572	Punctal stenosis
HP:0025608	Cicatricial ectropion
HP:0025809	Generalized scaling
HP:0025813	Eyebrow scaling skin
HP:0030001	Lagophthalmos
HP:0030053	Stiff skin
HP:0031057	Skin fissure
HP:0033665	Diminished health-related quality of life
HP:0100583	Corneal perforation
HP:0100679	Lack of skin elasticity
HP:0100806	Sepsis
HP:0100840	Aplasia/Hypoplasia of the eyebrow

GWAS associations

1 associations:

Study	Trait	p-value
GCST002481_1	Acne (severe)	5e-6

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C537263	Lamellar ichthyosis, autosomal dominant form *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases expression, decreases expression, decreases methylation	3
Benzo(a)pyrene	decreases expression, increases methylation, increases mutagenesis	3
Diethylhexyl Phthalate	increases abundance, decreases expression, decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression, affects cotreatment	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression, increases abundance	1
tris(2-butoxyethyl) phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
hydroquinone	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
abrine	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, decreases expression	1
Cadmium	decreases expression, increases abundance	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Quercetin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	Phase 4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	Phase 4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	Phase 4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	Phase 4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	Phase 4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	Phase 4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	Phase 4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	Phase 4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	Phase 4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	Phase 4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	Phase 4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	Phase 4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	Phase 4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	Phase 4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	Phase 4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	Phase 4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	Phase 4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	Phase 4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	Phase 4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	Phase 4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	Phase 4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	Phase 4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	Phase 4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	Phase 4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	Phase 4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	Phase 4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	Phase 4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	Phase 4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	Phase 4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	Phase 4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	Phase 4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	Phase 4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	Phase 4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	Phase 4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	Phase 4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	Phase 4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	Phase 4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	Phase 4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	Phase 4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer
NCT01673984	Phase 4	TERMINATED	GP Extended Action Triptorelin
NCT01753297	Phase 4	COMPLETED	A Study of Immediate 9 Months Adjuvant Hormone Therapy With Triptorelin 11.25 mg Versus Active Surveillance After Radical Prostatectomy in High Risk Prostate Cancer Patients.
NCT01794793	Phase 4	COMPLETED	Study to Allow Access to Pasireotide for Patients Benefiting From Pasireotide Treatment in Novartis-sponsored Studies
NCT01950871	Phase 4	TERMINATED	Prostate Guided Biopsy Study Evaluating the Diagnostic Performance of Prostate HistoScanning
NCT01995513	Phase 4	COMPLETED	Safety Study of Continued Enzalutamide Treatment In Prostate Cancer Patients
NCT02102646	Phase 4	COMPLETED	MRI Substudy; Metabolic Changes Due to Iatrogenic Hypogonadism
NCT02116582	Phase 4	COMPLETED	A Study to Evaluate Enzalutamide After Abiraterone in Metastatic Castration-Resistant Prostate Cancer
NCT02149628	Phase 4	COMPLETED	The Effect of Propofol Based Total Intravenous Anesthesia on Oxidative Stress and Nitric Oxide
NCT02405858	Phase 4	COMPLETED	A Study of Abiraterone Acetate in Metastatic Castration-Resistant Prostate Cancer Participants Who Responded Poorly to the First-line Combined Androgen Blockade Therapy
NCT02441517	Phase 4	TERMINATED	A Study of Enzalutamide Re-treatment in Metastatic Castration-resistant Prostate Cancer After Docetaxel and/or Cabazitaxel Treatment
NCT02441894	Phase 4	COMPLETED	Combination of Cabazitaxel With Prednisolone With Primary Prophylaxis With PEG-G-CSF in Treatment of Patients With Prostate Cancer
NCT02475057	Phase 4	COMPLETED	Endothelial Function in Prostate Cancer Patients on Degarelix vs. Luteinizing Hormone-Releasing Hormone Agonists
NCT02511665	Phase 4	UNKNOWN	Metformin And Longevity
NCT02651948	Phase 4	COMPLETED	Transperineal, MRI-guided, Prostate Biopsy
NCT02721433	Phase 4	COMPLETED	4-weekly Versus 12-weekly Administration of Bone-targeted Agents in Patients With Bone Metastases
NCT02726009	Phase 4	COMPLETED	A Trial to Evaluate Safety of Firmagon® (Degarelix) in Indian Patients Diagnosed With Advanced Hormone-dependent Prostate Cancer
NCT02749825	Phase 4	TERMINATED	Comparison of Trelstar Versus Lupron or Zoladex in Advanced Prostate Cancer
NCT02757365	Phase 4	UNKNOWN	Efficiency Study of Aspirin to Prevent the Occurrence of Prostate Cancer
NCT02773251	Phase 4	COMPLETED	The Effect of Guardix-solution for the Prevention of Postoperative Intestinal Adhesion and Intestinal Obstruction After Laparoscopic Pelvic Cavity Surgery
NCT02812186	Phase 4	COMPLETED	Deep Versus Moderate Neuromuscular Blockade During Laparoscopic Surgery