ZNFX1

Summary

ZNFX1 (zinc finger NFX1-type containing 1, HGNC:29271) is a protein-coding gene on chromosome 20q13.13, encoding NFX1-type zinc finger-containing protein 1 (Q9P2E3). RNA-binding protein that initiates the antiviral response and is required to restrict the replication of RNA viruses.

Enables RNA binding activity. Involved in defense response to bacterium and defense response to virus. Is active in cytoplasmic stress granule. Implicated in immunodeficiency 91.

Source: NCBI Gene 57169 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 91 and hyperinflammation (Strong, GenCC)
• GWAS associations: 40
• Clinical variants (ClinVar): 311 total — 8 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 45
• MANE Select transcript: NM_021035

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29271
Approved symbol	ZNFX1
Name	zinc finger NFX1-type containing 1
Location	20q13.13
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1404, FLJ11277
Ensembl gene	ENSG00000124201
Ensembl biotype	protein_coding
OMIM	618931
Entrez	57169

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000371744, ENST00000371752, ENST00000371754, ENST00000396105, ENST00000455070, ENST00000469991

RefSeq mRNA: 1 — MANE Select: NM_021035 NM_021035

CCDS: CCDS13417

Canonical transcript exons

ENST00000396105 — 14 exons

Exon	Start	End
ENSE00001456032	49278021	49278057
ENSE00001523886	49245900	49249711
ENSE00003888844	49251527	49251622
ENSE00003889784	49264716	49264864
ENSE00003889797	49266135	49266266
ENSE00003891284	49260463	49260577
ENSE00003891935	49275779	49275887
ENSE00003892404	49254495	49254649
ENSE00003892532	49263334	49263483
ENSE00003892558	49255808	49255947
ENSE00003893719	49269942	49271750
ENSE00003893942	49257417	49257664
ENSE00003894124	49253666	49253811
ENSE00003894182	49252720	49252830

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 96.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.7047 / max 770.8726, expressed in 1820 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187733	32.4223	1808
187735	4.2583	1291
187734	0.0242	2

Top tissues by expression

255 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	96.84	gold quality
left ventricle myocardium	UBERON:0006566	96.31	gold quality
cartilage tissue	UBERON:0002418	93.95	gold quality
nasal cavity epithelium	UBERON:0005384	93.65	gold quality
upper arm skin	UBERON:0004263	92.96	gold quality
pancreatic ductal cell	CL:0002079	92.21	silver quality
decidua	UBERON:0002450	92.04	gold quality
myocardium	UBERON:0002349	91.90	gold quality
tibialis anterior	UBERON:0001385	91.81	silver quality
saphenous vein	UBERON:0007318	91.60	gold quality
blood	UBERON:0000178	91.52	gold quality
kidney epithelium	UBERON:0004819	91.09	gold quality
calcaneal tendon	UBERON:0003701	90.39	gold quality
lower lobe of lung	UBERON:0008949	90.30	gold quality
layer of synovial tissue	UBERON:0007616	89.85	gold quality
epithelial cell of pancreas	CL:0000083	89.45	gold quality
ileal mucosa	UBERON:0000331	89.38	gold quality
stromal cell of endometrium	CL:0002255	89.04	gold quality
synovial joint	UBERON:0002217	89.00	gold quality
palpebral conjunctiva	UBERON:0001812	88.89	gold quality
cardia of stomach	UBERON:0001162	88.68	gold quality
vena cava	UBERON:0004087	88.64	gold quality
superficial temporal artery	UBERON:0001614	88.51	gold quality
deltoid	UBERON:0001476	88.18	gold quality
granulocyte	CL:0000094	87.64	gold quality
epithelium of nasopharynx	UBERON:0001951	87.61	gold quality
nipple	UBERON:0002030	87.56	gold quality
tendon	UBERON:0000043	87.53	gold quality
urethra	UBERON:0000057	87.48	gold quality
bone marrow cell	CL:0002092	87.42	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7052	no	570.80
E-MTAB-6142	no	269.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

108 targeting ZNFX1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687

Literature-anchored findings (GeneRIF, showing 9)

• MAD-CaP-5 (KIAA1404) is a novel prostate cancer antigen. (PMID:15838384)
• long noncoding RNA ZNFX1 antisense RNA expression was lower in survivor group compared to nonsurvivor group, and it presented with a good predictive value on distinguishing nonsurvivors from survivors in sepsis patients. (PMID:30817573)
• This study suggests a regulatory network in which ZFAS1 is capable of enhancing c-Myc expression by inducing the expression of YAP1, TEAD1, and KDM3A through crosstalk with their upstream miRNAs, thereby globally promoting prostate cancer tumorigenesis. (PMID:31321444)
• LncRNA ZNFX1-AS1 targeting miR-193a-3p/SDC1 regulates cell proliferation, migration and invasion of bladder cancer cells. (PMID:32432735)
• Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency. (PMID:33872655)
• Inherited deficiency of stress granule ZNFX1 in patients with monocytosis and mycobacterial disease. (PMID:33876776)
• Biallelic ZNFX1 variants are associated with a spectrum of immuno-hematological abnormalities. (PMID:34708404)
• Long non-coding RNA ZNFX1 antisense 1 (ZFAS1) suppresses anti-oxidative stress in chondrocytes during osteoarthritis by sponging microRNA-1323. (PMID:35635081)
• Circular RNA CircSATB2 facilitates osteosarcoma progression through regulating the miR-661/FUS-mediated mRNA of ZNFX1. (PMID:37984605)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	znfx1	ENSDARG00000100280
mus_musculus	Znfx1	ENSMUSG00000039501
rattus_norvegicus	Znfx1	ENSRNOG00000008194
drosophila_melanogaster	CG6204	FBGN0039165
caenorhabditis_elegans	Y106G6D.5	WBGENE00014965
caenorhabditis_elegans	sosi-1	WBGENE00016565
caenorhabditis_elegans	eri-7	WBGENE00016566

Paralogs (10): UPF1 (ENSG00000005007), AQR (ENSG00000021776), MOV10L1 (ENSG00000073146), SETX (ENSG00000107290), HELZ2 (ENSG00000130589), IGHMBP2 (ENSG00000132740), DNA2 (ENSG00000138346), MOV10 (ENSG00000155363), CT55 (ENSG00000169551), HELZ (ENSG00000198265)

Protein

Protein identifiers

NFX1-type zinc finger-containing protein 1 — Q9P2E3 (reviewed: Q9P2E3)

All UniProt accessions (4): Q9P2E3, Q5JXR5, Q5JXR6, Q5JXR7

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that initiates the antiviral response and is required to restrict the replication of RNA viruses. Acts as a double-stranded RNA (dsRNA) sensor that recognizes viral RNA and then interacts with MAVS to initiate the type I interferon response. Also required for immunity against some bacteria, such as mycobacteria.

Subunit / interactions. Interacts with MAVS.

Subcellular location. Mitochondrion outer membrane. Cytoplasm. Stress granule.

Tissue specificity. Widely expressed.

Disease relevance. Immunodeficiency 91 and hyperinflammation (IMD91) [MIM:619644] An autosomal recessive disorder characterized by immunodeficiency, recurrent infections, and hyperinflammation with systemic involvement. Most patients eventually develop hepatic or renal failure, may have compromised neurologic function, lymphadenopathy or hepatosplenomegaly. Early death often occurs due to multiorgan failure. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ZNFX1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P2E3-1	1	yes
Q9P2E3-2	2

RefSeq proteins (1): NP_066363* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000967	Znf_NFX1	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041677	DNA2/NAM7_AAA_11	Domain
IPR041679	DNA2/NAM7-like_C	Domain
IPR045055	DNA2/NAM7-like	Family
IPR046439	ZF_RZ_dom	Domain
IPR047187	SF1_C_Upf1	Domain
IPR057373	ZNFX1	Domain

Pfam: PF13086, PF13087, PF20173, PF25396

UniProt features (47 total): sequence variant 13, zinc finger region 7, sequence conflict 7, compositionally biased region 6, region of interest 4, binding site 4, coiled-coil region 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9EVE	X-RAY DIFFRACTION	3.67
9Q9Z	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2E3-F1	74.02	0.15

Functional residue map

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

Ligand- & substrate-binding residues (4): 1849; 1853; 1869; 1872

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 425 (showing top): TGCGCANK_UNKNOWN, PID_TELOMERASE_PATHWAY, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, CTATGCA_MIR153, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, MODULE_239, WANG_LMO4_TARGETS_DN, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_VIRAL_GENOME_REPLICATION, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_VIRAL_LIFE_CYCLE

GO Biological Process (7): activation of innate immune response (GO:0002218), regulatory ncRNA-mediated heterochromatin formation (GO:0031048), defense response to bacterium (GO:0042742), negative regulation of viral genome replication (GO:0045071), innate immune response (GO:0045087), defense response to virus (GO:0051607), immune system process (GO:0002376)

GO Molecular Function (4): RNA binding (GO:0003723), helicase activity (GO:0004386), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (7): mitochondrial outer membrane (GO:0005741), cytoplasmic stress granule (GO:0010494), nuclear RNA-directed RNA polymerase complex (GO:0031380), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
activation of immune response	1
positive regulation of innate immune response	1
regulatory ncRNA-mediated gene silencing	1
heterochromatin formation	1
response to bacterium	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
immune response	1
defense response to symbiont	1
response to virus	1
biological_process	1
nucleic acid binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
ATP-dependent activity	1
transition metal ion binding	1
cation binding	1
mitochondrial membrane	1
organelle outer membrane	1
cytoplasmic ribonucleoprotein granule	1
RNA-directed RNA polymerase complex	1
nuclear protein-containing complex	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

884 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNFX1	NFX1	Q12986	593
ZNFX1	PARP12	Q9H0J9	580
ZNFX1	USP18	Q9UMW8	550
ZNFX1	CMPK2	Q5EBM0	549
ZNFX1	MX1	P20591	501
ZNFX1	IFIH1	Q9BYX4	498
ZNFX1	TRIM25	Q14258	483
ZNFX1	IFIT5	Q13325	481
ZNFX1	EIF2AK2	P19525	480
ZNFX1	STAT2	P52630	480
ZNFX1	NRDE2	Q9H7Z3	469
ZNFX1	MUL1	Q969V5	458
ZNFX1	MAVS	Q7Z434	449
ZNFX1	IRF7	Q92985	442
ZNFX1	PABPC1	P11940	437

IntAct

51 interactions, top by confidence:

A	B	Type	Score
CDK4	CCND3	psi-mi:“MI:0914”(association)	0.980
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
STRAP	CDK2AP1	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ZNFX1		psi-mi:“MI:0915”(physical association)	0.370
ZNFX1	UBE2D1	psi-mi:“MI:0915”(physical association)	0.370
ZNFX1	UBE2D2	psi-mi:“MI:0915”(physical association)	0.370
ZNFX1	UBE2D4	psi-mi:“MI:0915”(physical association)	0.370
MEGF10	ZNFX1	psi-mi:“MI:0915”(physical association)	0.370
SCAF11	MRPL3	psi-mi:“MI:0914”(association)	0.350
ZNFX1	DRC1	psi-mi:“MI:0914”(association)	0.350
Ptbp1	MATR3	psi-mi:“MI:0914”(association)	0.350
CXXC4	TIA1	psi-mi:“MI:0914”(association)	0.350
Hsph1	USP9Y	psi-mi:“MI:0914”(association)	0.350
HSF2	RBBP6	psi-mi:“MI:0914”(association)	0.350
UGGT1	SF3B1	psi-mi:“MI:0914”(association)	0.350
PCDH1	DBI	psi-mi:“MI:0914”(association)	0.350
TUBA1C	TCP11L2	psi-mi:“MI:0914”(association)	0.350
PDK1	VWA8	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
	CLIC1	psi-mi:“MI:0914”(association)	0.350
STRAP	GEMIN2	psi-mi:“MI:0914”(association)	0.350
B4GALT2	LENG9	psi-mi:“MI:0914”(association)	0.350
FAM167A	IFT56	psi-mi:“MI:0914”(association)	0.350
MRPS17	RCCD1	psi-mi:“MI:0914”(association)	0.350
UBXN6	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
SULT1C4	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
CRYBB3	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
KLHL14	ARHGAP32	psi-mi:“MI:0914”(association)	0.350

BioGRID (76): ZNFX1 (Affinity Capture-RNA), ZNFX1 (Affinity Capture-RNA), ZNFX1 (Affinity Capture-RNA), ZNFX1 (Affinity Capture-RNA), ZNFX1 (Affinity Capture-MS), FYN (Affinity Capture-MS), CSDE1 (Affinity Capture-MS), DROSHA (Affinity Capture-MS), SS18L2 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), MIEF1 (Affinity Capture-MS), IMP3 (Affinity Capture-MS), DDX27 (Affinity Capture-MS), ZNFX1 (Affinity Capture-MS), ZNFX1 (Affinity Capture-MS)

ESM2 similar proteins: A1E2V0, A5D8Q0, A9JTP3, A9ULZ2, B1B1A0, O08863, O62640, P33279, P36406, P36407, P42573, P51784, P98170, Q13049, Q13075, Q13489, Q13490, Q1L8G6, Q24307, Q4R8E0, Q5BKL8, Q60989, Q62210, Q63185, Q6P5D3, Q6ZPS6, Q6ZUJ8, Q7Z2W4, Q80Z32, Q8C7M3, Q8CH72, Q8JHV9, Q8K337, Q8N1W1, Q8R151, Q90660, Q95M71, Q95M72, Q96P09, Q9BQI3

Diamond homologs: A0A0R4I9Y1, A0A0R4IBK5, E9Q555, Q2TBT8, Q63HN8, Q66JE4, Q6NZ21, Q6PJ69, Q8R151, Q96LD4, Q9P2E3, A0JMY5, A6QLA0, B1AY10, Q12986, Q18034, Q6ZNB6, Q9FFK8, Q9SY59, B6SFA4, D3ZG52, E1BMP7, E9QAM5, F1RCY6, O76512, O94247, O94387, P23249, P30771, P32644, P38935, P40694, P51530, Q00416, Q09449, Q09820, Q0V8H6, Q0VGT4, Q1LXK4, Q54I89

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	3
Uncertain significance	248
Likely benign	22
Benign	10

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1327517	NM_021035.3(ZNFX1):c.4815_4818del (p.Glu1606fs)	Pathogenic
1327518	NM_021035.3(ZNFX1):c.2876C>G (p.Ser959Ter)	Pathogenic
1327519	NM_021035.3(ZNFX1):c.495_496insT (p.Thr166fs)	Pathogenic
1327520	NM_021035.3(ZNFX1):c.2698_2699insT (p.Arg900fs)	Pathogenic
1327521	NM_021035.3(ZNFX1):c.1623_1624del (p.His542fs)	Pathogenic
1327522	NM_021035.3(ZNFX1):c.397A>T (p.Lys133Ter)	Pathogenic
1701423	NM_021035.3(ZNFX1):c.2793G>A (p.Trp931Ter)	Pathogenic
2155197	NM_021035.3(ZNFX1):c.1474C>T (p.Gln492Ter)	Pathogenic
3047510	NM_021035.3(ZNFX1):c.3313-2_3313-1del	Likely pathogenic
3778725	NM_021035.3(ZNFX1):c.4966_4969delinsTC (p.Glu1656fs)	Likely pathogenic
4077754	NM_021035.3(ZNFX1):c.561_562del (p.Ile187fs)	Likely pathogenic

SpliceAI

2691 predictions. Top by Δscore:

Variant	Effect	Δscore
20:49238943:A:AG	acceptor_gain	1.0000
20:49238943:ATT:A	acceptor_gain	1.0000
20:49238944:T:G	acceptor_gain	1.0000
20:49238945:T:TA	acceptor_gain	1.0000
20:49238946:GAGAT:G	acceptor_loss	1.0000
20:49238947:AGA:A	acceptor_loss	1.0000
20:49238948:G:GT	acceptor_loss	1.0000
20:49238948:GAT:G	acceptor_gain	1.0000
20:49239226:A:AG	acceptor_gain	1.0000
20:49239227:T:G	acceptor_gain	1.0000
20:49239232:A:AG	acceptor_gain	1.0000
20:49239233:C:G	acceptor_gain	1.0000
20:49239233:CAGAT:C	acceptor_loss	1.0000
20:49239234:A:AG	acceptor_gain	1.0000
20:49239235:G:A	acceptor_loss	1.0000
20:49239235:G:GA	acceptor_gain	1.0000
20:49239235:GA:G	acceptor_gain	1.0000
20:49239235:GAT:G	acceptor_gain	1.0000
20:49239235:GATC:G	acceptor_gain	1.0000
20:49239235:GATCA:G	acceptor_gain	1.0000
20:49239325:G:GT	donor_gain	1.0000
20:49239334:GAAAA:G	donor_gain	1.0000
20:49239335:AAAA:A	donor_gain	1.0000
20:49239336:AAA:A	donor_gain	1.0000
20:49239337:AA:A	donor_gain	1.0000
20:49239338:AGT:A	donor_loss	1.0000
20:49239339:G:GG	donor_gain	1.0000
20:49239348:G:GT	donor_gain	1.0000
20:49239349:G:T	donor_gain	1.0000
20:49241886:A:AG	acceptor_gain	1.0000

AlphaMissense

12731 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:49253691:A:G	L1027P	1.000
20:49248169:A:G	C1619R	0.999
20:49252763:C:G	R1058P	0.999
20:49252802:A:G	L1045P	0.999
20:49253749:C:G	A1008P	0.999
20:49253805:G:T	A989D	0.999
20:49253808:G:T	A988D	0.999
20:49253809:C:G	A988P	0.999
20:49254509:C:T	G982E	0.999
20:49266140:A:G	L666P	0.999
20:49266160:A:C	N659K	0.999
20:49266160:A:T	N659K	0.999
20:49266169:A:C	C656W	0.999
20:49270256:A:G	L519P	0.999
20:49270488:A:G	W442R	0.999
20:49270488:A:T	W442R	0.999
20:49270677:C:G	D379H	0.999
20:49270682:C:G	R377P	0.999
20:49270685:A:G	L376P	0.999
20:49270688:A:G	L375P	0.999
20:49248418:A:G	C1536R	0.998
20:49248472:A:G	C1518R	0.998
20:49249120:A:G	C1302R	0.998
20:49251618:C:G	R1074P	0.998
20:49252760:A:G	L1059P	0.998
20:49252784:A:G	L1051P	0.998
20:49252823:G:T	P1038H	0.998
20:49253745:G:T	A1009E	0.998
20:49253746:C:G	A1009P	0.998
20:49253763:A:T	V1003D	0.998

dbSNP variants (sampled 300 via entrez): RS1000042643 (20:49277336 G>C), RS1000070514 (20:49279695 T>C), RS1000085785 (20:49274637 T>C), RS1000262921 (20:49267456 C>T), RS1000314916 (20:49250983 A>G), RS1000589557 (20:49248119 G>C), RS1000603257 (20:49250725 T>C,G), RS1000653729 (20:49261820 A>C,G), RS1000659328 (20:49255399 C>G), RS1000702813 (20:49258040 C>A,T), RS1000906742 (20:49276264 G>A), RS1001026826 (20:49264600 C>T), RS1001239192 (20:49252068 A>G,T), RS1001249266 (20:49268864 A>G), RS1001285722 (20:49261639 A>G)

Disease associations

OMIM: gene MIM:618931 | disease phenotypes: MIM:619644

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 91 and hyperinflammation	Strong	Autosomal recessive

Mondo (1): immunodeficiency 91 and hyperinflammation (MONDO:0030491)

Orphanet (0):

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000100	Nephrotic syndrome
HP:0000729	Autistic behavior
HP:0000793	Membranoproliferative glomerulonephritis
HP:0000969	Edema
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001522	Death in infancy
HP:0001873	Thrombocytopenia
HP:0001954	Recurrent fever
HP:0002202	Pleural effusion
HP:0002240	Hepatomegaly
HP:0002254	Intermittent diarrhea
HP:0002384	Focal impaired awareness seizure
HP:0002480	Hepatic encephalopathy
HP:0002514	Cerebral calcification
HP:0002716	Lymphadenopathy
HP:0002783	Recurrent lower respiratory tract infections
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003565	Elevated erythrocyte sedimentation rate
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003819	Death in childhood
HP:0005548	Megakaryocytopenia
HP:0005575	Hemolytic-uremic syndrome
HP:0006530	Abnormal pulmonary interstitial morphology
HP:0006532	Recurrent pneumonia

GWAS associations

40 associations (top):

Study	Trait	p-value
GCST000817_197	Height	1.000000e-20
GCST002646_11	Infant length	1.000000e-09
GCST006269_812	General cognitive ability	8.000000e-09
GCST006923_15	Loneliness	3.000000e-08
GCST006924_7	Loneliness (MTAG)	3.000000e-09
GCST007044_24	Extremely high intelligence	7.000000e-10
GCST008163_1	Height	4.000000e-06
GCST010796_2415	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-23
GCST010796_2416	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-10
GCST010796_2417	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-12
GCST010796_2418	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-15
GCST010796_2419	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-20
GCST010796_2420	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-19
GCST010796_2421	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-19
GCST010796_2422	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-22
GCST010796_2423	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-17
GCST010796_2424	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-16
GCST010796_2425	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-21
GCST010796_2576	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-22
GCST010796_2577	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-19
GCST010796_2578	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-18
GCST010796_2579	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-18
GCST010796_2580	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-19
GCST010796_2581	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-18
GCST010796_2582	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-17
GCST010796_2583	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-17
GCST010796_2584	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-16
GCST010796_2585	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-15
GCST010796_2586	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-15
GCST010796_2587	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-15

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006785	infant body height
EFO:0004337	intelligence
EFO:0007865	loneliness measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	3
Nickel	increases expression	2
Aflatoxin B1	affects expression, increases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
2-butenal	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Cisplatin	increases expression	1
Demecolcine	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Gallic Acid	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Methyl Methanesulfonate	increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases expression	1
Vincristine	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.