AMZ1

Summary

AMZ1 (archaelysin family metallopeptidase 1, HGNC:22231) is a protein-coding gene on chromosome 7p22.3, encoding Archaemetzincin-1 (Q400G9). Probable zinc metalloprotease.

Predicted to enable metal ion binding activity and metallopeptidase activity. Predicted to be involved in proteolysis.

Source: NCBI Gene 155185 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 69 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 221 total — 2 pathogenic
• GTEx eGene: eQTL in 29 tissues, sQTL in 3 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.88 (unconstrained)
• MANE Select transcript: NM_001384743
• Notable: 221 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22231
Approved symbol	AMZ1
Name	archaelysin family metallopeptidase 1
Location	7p22.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1950
Ensembl gene	ENSG00000174945
Ensembl biotype	protein_coding
OMIM	615168
Entrez	155185

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 11 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000683327

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

ENST00000683327, ENST00000312371, ENST00000407112, ENST00000433945, ENST00000480560, ENST00000485540, ENST00000489665, ENST00000880039, ENST00000880040, ENST00000880041, ENST00000880042, ENST00000954549, ENST00000974156, ENST00000974157, ENST00001118455, ENST00001139114

RefSeq mRNA: 8 — MANE Select: NM_001384743 NM_001284355, NM_001321766, NM_001384739, NM_001384740, NM_001384741, NM_001384742, NM_001384743, NM_133463

CCDS: CCDS34589, CCDS64582

Canonical transcript exons

ENST00000683327 — 7 exons

Exon	Start	End
ENSE00001181977	2709075	2709244
ENSE00001264348	2700234	2700755
ENSE00001563758	2688202	2688296
ENSE00003474761	2708588	2708716
ENSE00003602694	2702722	2702889
ENSE00003654718	2709640	2709816
ENSE00003918174	2712330	2719683

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 78.25.

FANTOM5 (CAGE): breadth broad, TPM avg 1.8966 / max 33.2578, expressed in 450 samples.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, amygdala, stromal cell of endometrium, sperm, primordial germ cell in gonad.

Genetic regulation across tissues (GTEx eQTL / sQTL)

AMZ1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 32 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Lung	eqtl	9.2e-105	+1.25	7:2694042:A:G
Thyroid	eqtl	7.0e-49	+0.73	7:2712054:T:TAAAAAA
Spleen	eqtl	1.3e-18	+0.82	7:2687585:C:G
Liver	eqtl	5.9e-17	+0.77	7:2679481:G:A
Cells EBV-transformed lymphocytes	eqtl	1.3e-07	+0.44	7:2842283:A:G
Brain Nucleus accumbens basal ganglia	eqtl	1.8e-07	+0.39	7:2823257:C:T
Brain Caudate basal ganglia	eqtl	4.4e-07	+0.34	7:2707008:G:C
Brain Cortex	eqtl	1.3e-06	-0.32	7:2718524:G:A
Heart Atrial Appendage	eqtl	1.3e-05	+0.25	7:2823655:A:C
Cells Cultured fibroblasts	eqtl	2.2e-05	+0.24	7:2689875:C:T
Testis	sqtl	3.1e-05	+0.47	7:2823940:G:A
Esophagus Muscularis	eqtl	3.5e-05	-0.26	7:2654288:A:G
Brain Frontal Cortex BA9	eqtl	4.9e-05	+0.26	7:2704818:G:A
Brain Putamen basal ganglia	eqtl	5.5e-05	+0.35	7:2709535:T:C
Brain Anterior cingulate cortex BA24	eqtl	2.0e-04	-0.36	7:2721116:C:A
Brain Hippocampus	eqtl	2.2e-04	-0.26	7:2704243:A:C
Adipose Visceral Omentum	eqtl	3.0e-04	+0.27	7:2822908:C:A
Brain Cerebellum	eqtl	3.4e-04	+0.47	7:2693657:T:G
Brain Caudate basal ganglia	sqtl	4.9e-04	+0.54	7:2712518:G:A
Brain Cerebellar Hemisphere	eqtl	5.1e-04	+0.43	7:2693648:C:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
77027	1.8966	450

Top tissues by expression

showing 100 of 227 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.25	gold quality
amygdala	UBERON:0001876	73.99	gold quality
stromal cell of endometrium	CL:0002255	73.49	gold quality
sperm	CL:0000019	73.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.92	gold quality
prefrontal cortex	UBERON:0000451	71.51	gold quality
nucleus accumbens	UBERON:0001882	71.23	gold quality
sural nerve	UBERON:0015488	71.03	gold quality
anterior cingulate cortex	UBERON:0009835	70.97	gold quality
midbrain	UBERON:0001891	70.27	gold quality
substantia nigra	UBERON:0002038	70.23	gold quality
ventricular zone	UBERON:0003053	70.11	gold quality
putamen	UBERON:0001874	69.95	gold quality
lateral globus pallidus	UBERON:0002476	69.90	silver quality
corpus callosum	UBERON:0002336	69.81	gold quality
vena cava	UBERON:0004087	69.81	gold quality
pericardium	UBERON:0002407	69.78	gold quality
superior vestibular nucleus	UBERON:0007227	69.63	gold quality
cerebellar vermis	UBERON:0004720	69.51	gold quality
body of tongue	UBERON:0011876	69.37	gold quality
tongue	UBERON:0001723	69.36	gold quality
nipple	UBERON:0002030	69.35	gold quality
superior surface of tongue	UBERON:0007371	69.30	gold quality
pharyngeal mucosa	UBERON:0000355	69.21	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	69.14	gold quality
substantia nigra pars compacta	UBERON:0001965	69.06	silver quality
hypothalamus	UBERON:0001898	68.97	gold quality
medulla oblongata	UBERON:0001896	68.93	gold quality
saphenous vein	UBERON:0007318	68.89	gold quality
temporal lobe	UBERON:0001871	68.76	gold quality
renal medulla	UBERON:0000362	68.69	gold quality
trigeminal ganglion	UBERON:0001675	68.60	gold quality
synovial joint	UBERON:0002217	68.58	gold quality
pons	UBERON:0000988	68.52	gold quality
pylorus	UBERON:0001166	68.46	gold quality
neocortex	UBERON:0001950	68.45	gold quality
trachea	UBERON:0003126	68.36	gold quality
frontal cortex	UBERON:0001870	68.33	gold quality
colonic epithelium	UBERON:0000397	68.26	silver quality
layer of synovial tissue	UBERON:0007616	68.13	gold quality
nasal cavity epithelium	UBERON:0005384	67.96	gold quality
caudate nucleus	UBERON:0001873	67.89	gold quality
right frontal lobe	UBERON:0002810	67.67	gold quality
decidua	UBERON:0002450	67.52	silver quality
superficial temporal artery	UBERON:0001614	67.49	gold quality
penis	UBERON:0000989	67.37	gold quality
cerebral cortex	UBERON:0000956	67.24	gold quality
Ammon’s horn	UBERON:0001954	67.23	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	67.15	gold quality
forebrain	UBERON:0001890	67.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.87	gold quality
oocyte	CL:0000023	66.37	silver quality
occipital lobe	UBERON:0002021	66.32	gold quality
brain	UBERON:0000955	66.02	gold quality
medial globus pallidus	UBERON:0002477	65.93	silver quality
epithelium of nasopharynx	UBERON:0001951	65.78	gold quality
gingival epithelium	UBERON:0001949	65.48	gold quality
parotid gland	UBERON:0001831	65.45	gold quality
quadriceps femoris	UBERON:0001377	65.36	gold quality
bone marrow cell	CL:0002092	65.27	silver quality
vastus lateralis	UBERON:0001379	65.23	gold quality
primary visual cortex	UBERON:0002436	65.02	gold quality
deltoid	UBERON:0001476	64.88	gold quality
gingiva	UBERON:0001828	64.15	gold quality
spinal cord	UBERON:0002240	63.87	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	63.29	gold quality
ganglionic eminence	UBERON:0004023	63.27	gold quality
adrenal tissue	UBERON:0018303	62.86	gold quality
skin of hip	UBERON:0001554	62.80	gold quality
biceps brachii	UBERON:0001507	62.68	gold quality
bone marrow	UBERON:0002371	62.67	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	62.61	gold quality
upper leg skin	UBERON:0004262	62.48	gold quality
parietal lobe	UBERON:0001872	62.38	gold quality
superior frontal gyrus	UBERON:0002661	62.14	gold quality
uterine cervix	UBERON:0000002	62.08	gold quality
tonsil	UBERON:0002372	61.99	gold quality
Brodmann (1909) area 23	UBERON:0013554	61.94	gold quality
heart right ventricle	UBERON:0002080	61.87	gold quality
cartilage tissue	UBERON:0002418	61.83	silver quality
mammalian vulva	UBERON:0000997	60.77	gold quality
skeletal muscle tissue	UBERON:0001134	60.69	gold quality
mucosa of paranasal sinus	UBERON:0005030	60.67	gold quality
endocervix	UBERON:0000458	60.66	gold quality
postcentral gyrus	UBERON:0002581	60.59	gold quality
buccal mucosa cell	CL:0002336	60.26	silver quality
muscle tissue	UBERON:0002385	59.95	gold quality
smooth muscle tissue	UBERON:0001135	59.80	gold quality
mammary duct	UBERON:0001765	59.59	gold quality
myometrium	UBERON:0001296	59.38	gold quality
oviduct epithelium	UBERON:0004804	59.37	silver quality
trabecular bone tissue	UBERON:0002483	59.05	gold quality
liver	UBERON:0002107	58.96	gold quality
oral cavity	UBERON:0000167	58.62	gold quality
tibia	UBERON:0000979	58.60	silver quality
placenta	UBERON:0001987	58.42	gold quality
left testis	UBERON:0004533	58.39	gold quality
uterus	UBERON:0000995	58.20	gold quality
right testis	UBERON:0004534	57.89	gold quality
testis	UBERON:0000473	57.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.89

HPA expression

RNA tissue specificity: Tissue enhanced

56 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Nucleus accumbens	tissue	16.5
Caudate putamen	tissue	15.2
Hippocampus	tissue	15.0
Basal ganglia	tissue	14.5
Amygdala	tissue	14.0
Cerebral cortex	tissue	13.1
Insular cortex	tissue	13.1
Motor cortex	tissue	12.5
Temporal cortex	tissue	12.5
Prefrontal cortex	tissue	11.7
Postcentral gyrus	tissue	11.2
Olfactory bulb	tissue	11.2
Hippocampal formation	tissue	10.8
Septum	tissue	10.7
Entorhinal cortex	tissue	10.4
Retrosplenial and cingulate cortex	tissue	10.4
Retrosplenial cortex	tissue	10.0
Ventral forebrain	tissue	9.7
Locus coeruleus	tissue	9.6
Somatosensory cortex	tissue	9.3
Frontal cortex	tissue	9.0
Occipital cortex	tissue	7.4
Putamen	tissue	6.6
Hypothalamus	tissue	6.4
Substantia nigra	tissue	6.2
Periaqueductal gray	tissue	4.1
Pons	tissue	3.7
Midbrain	tissue	3.3
Medulla oblongata	tissue	2.8
Thalamus	tissue	2.7
Corpus callosum	tissue	2.7
Superior colliculi	tissue	2.4
Choroid plexus	tissue	2.0
Spinal cord	tissue	2.0
Cerebellum	tissue	1.5
Endometrium 1	tissue	0.7
Placenta	tissue	0.7
Smooth muscle	tissue	0.6
Lung	tissue	0.4
Bone marrow	tissue	0.4
Cervix	tissue	0.3
Ovary	tissue	0.3
Spleen	tissue	0.3
Tonsil	tissue	0.3
Lymph node	tissue	0.2
Testis	tissue	0.2
Fallopian tube	tissue	0.2
Appendix	tissue	0.2
Pituitary gland	tissue	0.1
Heart muscle	tissue	0.1
Retina	tissue	0.1
Vagina	tissue	0.1
Pancreas	tissue	0.1
Liver	tissue	0.1
Gallbladder	tissue	0.1
Duodenum	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Claustrum (24.1), Basal amygdala (23.6), Corticomedial amygdala (22.4), Ventral posterolateral thalamic nucleus (21.1), Posterior thalamic nucleus (20.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting AMZ1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 73 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-18A-3P	99.56	65.68	1092

Functional genomics

gnomAD constraint: pLI 4.2e-19, LOEUF 1.88, missense Z -5.68 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000683327 — one region, missense o/e 1.53.

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Amz1	ENSMUSG00000050022
rattus_norvegicus	Amz1	ENSRNOG00000077699

Paralogs (1): AMZ2 (ENSG00000196704)

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
Pongo abelii	Q5R4A6	97.5%	Diamond
Macaca fascicularis	Q4R684	96.4%	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
CARD11-AS1	ncRNA	101927256
GNA12	protein-coding	2768
TTYH3	protein-coding	80727
CARD11	protein-coding	84433
MIR4648	ncRNA	100616116
BRAT1	protein-coding	221927
IQCE	protein-coding	23288
LFNG	protein-coding	3955

Protein

Protein identifiers

Archaemetzincin-1 — Q400G9 (reviewed: Q400G9)

Alternative names: Archeobacterial metalloproteinase-like protein 1

All UniProt accessions (2): A4D202, Q400G9

UniProt curated annotations — full annotation on UniProt →

Function. Probable zinc metalloprotease.

Cofactor. Binds 2 Zn(2+) ions per subunit. One is catalytic, whereas the other seems to have a structural role.

Similarity. Belongs to the peptidase M54 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q400G9-1	1	yes
Q400G9-2	2

RefSeq proteins (8): NP_001271284, NP_001308695, NP_001371668, NP_001371669, NP_001371670, NP_001371671, NP_001371672, NP_597720 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012962	Pept_M54_archaemetzincn	Family
IPR024079	MetalloPept_cat_dom_sf	Homologous_superfamily
IPR052009	Archaemetzincin	Family

UniProt features (12 total): binding site 6, splice variant 2, chain 1, region of interest 1, sequence variant 1, active site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q400G9-F1	74.62	0.54

Human Protein Atlas

Protein class: Enzymes, Peptidases, Metallopeptidases, Predicted intracellular proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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
262	proton acceptor

Ligand- & substrate-binding residues (6)

Position	Role
261	Zn(2+)
265	Zn(2+)
272	Zn(2+)
277	Zn(2+)
296	Zn(2+)
299	Zn(2+)

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: 104 (showing top): GOMF_METALLOPEPTIDASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, chr7p22, NIKOLSKY_BREAST_CANCER_7P22_AMPLICON, BOYLAN_MULTIPLE_MYELOMA_C_D_UP, GOBP_PROTEOLYSIS, GOMF_PEPTIDASE_ACTIVITY, CHEN_METABOLIC_SYNDROM_NETWORK, DUTERTRE_ESTRADIOL_RESPONSE_6HR_UP, DUTERTRE_ESTRADIOL_RESPONSE_24HR_UP, BHAT_ESR1_TARGETS_NOT_VIA_AKT1_UP, BHAT_ESR1_TARGETS_VIA_AKT1_UP, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_UP, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_129_MOUSE_UP, GSE13522_CTRL_VS_T_CRUZI_Y_STRAIN_INF_SKIN_IFNAR_KO_UP

GO Biological Process (1): proteolysis (GO:0006508)

GO Molecular Function (4): metallopeptidase activity (GO:0008237), metal ion binding (GO:0046872), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (1): cellular_component (GO:0005575)

GO top-level categories

6 GO namespaces:

Category	Terms
protein metabolic process	1
peptidase activity	1
cation binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1

Protein interactions and networks

STRING

showing 15 of 466 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMZ1	BRAT1	Q6PJG6	481
AMZ1	CCDC71	Q8IV32	459
AMZ1	CCDC57	Q2TAC2	455
AMZ1	FASTKD3	Q14CZ7	446
AMZ1	OR6T1	Q8NGN1	446
AMZ1	DNAJC12	Q9UKB3	435
AMZ1	TTYH3	Q9C0H2	435
AMZ1	RDM1	Q8NG50	430
AMZ1	RAPGEFL1	Q9UHV5	427
AMZ1	STK31	Q9BXU1	416
AMZ1	CMYA5	Q8N3K9	406
AMZ1	MANEAL	Q5VSG8	400
AMZ1	MESP2	Q0VG99	394
AMZ1	FTSJ3	Q8IY81	374
AMZ1	NKAIN4	Q8IVV8	372

IntAct

Human interaction partners of AMZ1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
SUSD5	association	0.530	2
IFT56	association	0.350	1

BioGRID (55 interactions; top human partners by supporting records): ABI1 (Affinity Capture-MS; 2 records), ABI2 (Affinity Capture-MS; 2 records), BRK1 (Affinity Capture-MS; 2 records), CYFIP1 (Affinity Capture-MS; 2 records), CYFIP2 (Affinity Capture-MS; 2 records), NCKAP1 (Affinity Capture-MS; 2 records), NHSL1 (Affinity Capture-MS; 2 records), POLD2 (Affinity Capture-MS; 2 records), SUSD5 (Affinity Capture-MS; 2 records), WASF1 (Affinity Capture-MS; 2 records), WASF2 (Affinity Capture-MS; 2 records), AIFM1 (Affinity Capture-MS), ANAPC7 (Affinity Capture-MS), AP5B1 (Affinity Capture-MS), CEP97 (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for AMZ1: 221 ClinVar records (2 pathogenic / likely pathogenic); 69 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	172
Likely benign	18
Benign	11

Top pathogenic / likely-pathogenic (2)

Showing all 2 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
3245808	NC_000007.13:g.(?2559496)(2998140_?)del	Pathogenic	criteria provided, single submitter	1
443024	GRCh37/hg19 7p22.3-22.1(chr7:1201674-5175651)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore AMZ1’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; 29 predictions of 1,079):

Position(s)	Effect	Δscore	Sites
7:2702720	acceptor_loss	1.0000	2
7:2702890–2702891	donor_loss	1.0000	4
7:2708586	acceptor_loss	1.0000	3
7:2688297–2688298	donor_loss	0.9900	4
7:2700752	donor_gain	0.9900
7:2700756–2700757	donor_loss	0.9900	5
7:2702720–2702721	acceptor_loss	0.9900	2
7:2708587	acceptor_loss	0.9900	2
7:2708697	donor_gain	0.9900
7:2708717–2708718	donor_loss	0.9900	5

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene MIM:615168 | disease phenotypes: MIM:615206, MIM:616452

GenCC curated gene-disease

Mondo (2): severe combined immunodeficiency due to CARD11 deficiency (MONDO:0014081), BENTA disease (MONDO:0014645)

Orphanet (2): Combined immunodeficiency due to CARD11 deficiency (Orphanet:357237), BENTA disease (Orphanet:464336)

GWAS associations

showing 30 of 69 associations:

Study	Trait	p-value
GCST90000025_1028	Appendicular lean mass	3e-68
GCST008839_452	Height	3e-55
GCST007294_122	Body fat distribution (trunk fat ratio)	3e-43
GCST007295_77	Body fat distribution (leg fat ratio)	3e-40
GCST90020028_83	Hip circumference adjusted for BMI	8e-39
GCST007294_156	Body fat distribution (trunk fat ratio)	1e-38
GCST007295_55	Body fat distribution (leg fat ratio)	4e-37
GCST001956_32	Height	4e-23
GCST90002400_187	Plateletcrit	2e-20
GCST90020028_84	Hip circumference adjusted for BMI	9e-20
GCST012227_536	Hip circumference adjusted for BMI	3e-18
GCST010703_71	Brain morphology (MOSTest)	1e-17
GCST012227_548	Hip circumference adjusted for BMI	2e-17
GCST90002407_108	White blood cell count	2e-16
GCST012227_537	Hip circumference adjusted for BMI	9e-16
GCST012227_543	Hip circumference adjusted for BMI	4e-15
GCST90002393_586	Monocyte count	5e-15
GCST90020028_87	Hip circumference adjusted for BMI	8e-15
GCST012227_550	Hip circumference adjusted for BMI	3e-14
GCST90020028_142	Hip circumference adjusted for BMI	4e-14
GCST008362_198	Birth weight	3e-13
GCST012227_545	Hip circumference adjusted for BMI	3e-13
GCST007147_3	Lateral ventricular volume in normal aging	6e-13
GCST012227_540	Hip circumference adjusted for BMI	6e-13
GCST012227_544	Hip circumference adjusted for BMI	9e-13
GCST012227_546	Hip circumference adjusted for BMI	7e-12
GCST90020028_85	Hip circumference adjusted for BMI	7e-12
GCST012226_277	Waist circumference adjusted for body mass index	1e-11
GCST004133_28	Ulcerative colitis	4e-11
GCST90020028_86	Hip circumference adjusted for BMI	4e-11

EFO canonical traits (from GWAS)

18 canonical traits:

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008002	physical activity measurement
EFO:0009270	heel bone mineral density
EFO:0008487	lateral ventricle volume measurement
EFO:0004341	body fat distribution
EFO:0004338	body weight
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0008344	response to placebo
EFO:0010339	FVC change measurement
EFO:0004346	neuroimaging measurement
EFO:0006935	thalamus volume
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0004587	lymphocyte count
EFO:0005091	monocyte count
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
triphenyl phosphate	decreases expression	1
bisphenol A	decreases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
clothianidin	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Benzo(a)pyrene	decreases methylation, affects methylation	1
Doxorubicin	increases expression	1
Estradiol	increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Gold Compounds	increases expression	1
Antirheumatic Agents	decreases expression	1
Particulate Matter	decreases expression	1
Magnetite Nanoparticles	decreases methylation	1

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00076362	Phase 4	COMPLETED	Pediatric Hypothalamic Obesity
NCT00079547	Phase 4	COMPLETED	The Safety and Effectiveness of Low and High Carbohydrate Diets
NCT00115063	Phase 4	TERMINATED	LOSS- Louisiana Obese Subjects Study
NCT00134303	Phase 4	COMPLETED	Trial Comparing Metformin Versus Placebo in Non Alcoholic Steatohepatitis (NASH) Patients Receiving Bariatric Surgery for Obesity
NCT00143936	Phase 4	COMPLETED	The Safety and Efficacy of Low and High Carbohydrate Diets
NCT00143962	Phase 4	COMPLETED	Comparison of Two Approaches to Weight Loss Follow-Up Study
NCT00152360	Phase 4	COMPLETED	The Effect of Xenical on Weight and Risk Factors
NCT00176306	Phase 4	COMPLETED	Levofloxacin Pharmacokinetics (PK) in the Severely Obese
NCT00203450	Phase 4	COMPLETED	Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial
NCT00205504	Phase 4	COMPLETED	Oral Contraceptives in the Metabolic Syndrome
NCT00229229	Phase 4	TERMINATED	Comparison of 4 Diets in the Management of Overweight Patients With Vascular Disease
NCT00234988	Phase 4	COMPLETED	A Phase IV, Multi-Center, Open-Label Trial of Sibutramine in Combination With a Hypocaloric Diet in Obese and Overweight Thai Subjects.
NCT00264589	Phase 4	COMPLETED	Exercise Training and Cardiovascular Function in Obesity and in Type 2 Diabetes
NCT00288873	Phase 4	COMPLETED	Characterization of Hyperparathyroidism and Vitamin D Deficiency in Obesity
NCT00298857	Phase 4	TERMINATED	A Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights
NCT00315146	Phase 4	COMPLETED	Optimizing Body Composition for Function in Older Adults
NCT00319202	Phase 4	TERMINATED	Clinical Trial to Assess the Effects of Candesartan on the Carbohydrate Metabolism of Obese Subjects
NCT00327912	Phase 4	UNKNOWN	Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Biliopancreatic Diversion (BPD)- Duodenal Switch for Superobesity
NCT00352287	Phase 4	COMPLETED	Study to Determine the Effects of Human Growth Hormone and Pioglitazone in Overweight, Prediabetic Adults
NCT00353054	Phase 4	COMPLETED	Effect of Calcium/Vitamin D Supplementation on Body Weight and Fat Loss.
NCT00390637	Phase 4	COMPLETED	Diet, Obesity and Genes (DiOGenes)
NCT00415688	Phase 4	COMPLETED	Lifestyle Modification for Obesity-Related Type 2 Diabetes
NCT00433641	Phase 4	COMPLETED	Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes
NCT00440375	Phase 4	COMPLETED	Effects of Rosiglitazone on Bone in Postmenopausal Diabetic Women
NCT00453557	Phase 4	COMPLETED	Mechanism of Growth Hormone Effects on Adipose Tissue
NCT00456885	Phase 4	COMPLETED	The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
NCT00463112	Phase 4	COMPLETED	Effect of Diet Plus Sibutramine on Hormonal and Metabolic Features in Overweight and Obese Women With PCOS
NCT00512187	Phase 4	COMPLETED	Moderate Weight Loss Makes Obese Patients With Severe Chronic Plaque Psoriasis Responsive to Sub-Optimal Dose of Cyclosporine: an Investigator Blinded, Controlled, Randomized Clinical Trial
NCT00516919	Phase 4	COMPLETED	Study of Behavioral Weight Loss Therapy for Obesity and Binge Eating in Monolingual Hispanic Persons
NCT00522470	Phase 4	COMPLETED	Effects of Rosiglitazone on Serum Ghrelin and Peptide YY Levels
NCT00537810	Phase 4	COMPLETED	Treatment of Binge Eating in Obese Patients in Primary Care
NCT00538486	Phase 4	COMPLETED	A Randomized, Double-Blind, Active Control Trial Comparing Effects of Telmisartan, Candesartan and Amlodipine, Alone or Plus Metformin, on Non-Diabetic, Obese Hypertensive Patients
NCT00584389	Phase 4	TERMINATED	The Effect of Rimonabant on Energy Expenditure, Fat Metabolism and Body Composition
NCT00585182	Phase 4	COMPLETED	Study to Evaluate Weight-based Enoxaparin Dosing in Obese Medical Patients at Risk for DVT
NCT00632840	Phase 4	COMPLETED	Pharmacological Regulation of Fat Transport in Metabolic Syndrome
NCT00636142	Phase 4	COMPLETED	Effects of Infliximab on Insulin Sensitivity and Beta Cell Function in Insulin Resistant Human Obesity
NCT00675987	Phase 4	COMPLETED	A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients
NCT00694811	Phase 4	COMPLETED	Effects of Re-Feeding Duration on Weight Maintenance After Weight Loss With Very-Low-Energy Diets (VLEDs)
NCT00699413	Phase 4	TERMINATED	Supplements for Controlling Resistance to Insulin
NCT00729963	Phase 4	COMPLETED	Sibutramine Versus Continuous Positive Airway Pressure (CPAP)in Obstructive Sleep Apnea (OSA) Patients
NCT00752726	Phase 4	COMPLETED	Effect of Orlistat in Body Composition
NCT00770328	Phase 4	COMPLETED	The Effects of Pentoxifylline on PAI-1 in an Obese Population
NCT00775164	Phase 4	WITHDRAWN	Pioglitazone Therapy in Obese Children With Insulin Resistance: A Randomized, Controlled Pilot Study
NCT00775814	Phase 4	COMPLETED	Efficacy of Candesartan on Reducing Blood Pressure in Insulin-Resistant, Obese Patients With Hypertension.
NCT00779844	Phase 4	TERMINATED	Anesthesic Propofol and Remifentanil Requirements in Obese Patients
NCT00788840	Phase 4	COMPLETED	Detemir Energy Expenditure Study
NCT00790946	Phase 4	UNKNOWN	Kagoshima Collaborate Trial in Metabolic Syndrome (KACT Study)
NCT00841217	Phase 4	COMPLETED	Regulation of Lipoprotein Transport in Metabolic Syndrome
NCT00845559	Phase 4	WITHDRAWN	The Effects of Exenatide on Post-Meal Sugar Peaks and Vascular Health in Obese/Pre-Diabetic Young Adults
NCT00847262	Phase 4	COMPLETED	Trial Comparing Metabolic Effects of Telmisartan and Amlodipine on Hypertensive Patients With Obesity and Diabetes
NCT00852384	Phase 4	COMPLETED	Non Invasive Pressure Support Ventilation (NIPPV) Versus Recruitment Maneuver (RM) and Preoxygenation
NCT00877123	Phase 4	COMPLETED	Effect of Vitamin D Supplementation on Fasting Glucose and Interleukin-10 (IL-10) in Arab Women With Impaired Fasting Glucose
NCT00883259	Phase 4	UNKNOWN	Metformin and Gestational Diabetes in High-risk Patients: a RCTs
NCT00917033	Phase 4	COMPLETED	Tracheal Intubation of Morbidly Obese Patients. GlideScope Versus Direct Laryngoscopy
NCT00928005	Phase 4	COMPLETED	Evaluating the Effects of a Diet and Exercise Program in People With Type 2 Diabetes or Prediabetes: (The SHAPE3 Study)
NCT00932022	Phase 4	COMPLETED	Trospium Chloride XR in Obese Female Patients With Overactive Bladder
NCT00934570	Phase 4	COMPLETED	Activity and Metformin Intervention in Obese Adolescents
NCT00943969	Phase 4	COMPLETED	Determinants of Oral Morphine Answer Among Obese Patients Before and After Gastric Bypass
NCT00959309	Phase 4	COMPLETED	Media Use in Preschooler Study (MUPS)
NCT00983970	Phase 4	COMPLETED	Effects of Interactive Video Game Cycling on Obese Adolescent Health