RFXANK

Summary

RFXANK (regulatory factor X associated ankyrin containing protein, HGNC:9987) is a protein-coding gene on chromosome 19p13.11, encoding DNA-binding protein RFXANK (O14593). Activates transcription from class II MHC promoters.

Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune system. The protein encoded by this gene, along with regulatory factor X-associated protein and regulatory factor-5, forms a complex that binds to the X box motif of certain MHC class II gene promoters and activates their transcription. Once bound to the promoter, this complex associates with the non-DNA-binding factor MHC class II transactivator, which controls the cell type specificity and inducibility of MHC class II gene expression. This protein contains ankyrin repeats involved in protein-protein interactions. Mutations in this gene have been linked to bare lymphocyte syndrome type II, complementation group B. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 8625 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MHC class II deficiency (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 311 total — 14 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 56
• Transcription factor: yes — 21 downstream targets (CollecTRI)
• MANE Select transcript: NM_003721

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9987
Approved symbol	RFXANK
Name	regulatory factor X associated ankyrin containing protein
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	BLS, RFX-B, ANKRA1, F14150_1, MGC138628
Ensembl gene	ENSG00000064490
Ensembl biotype	protein_coding
OMIM	603200
Entrez	8625

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 25 protein_coding, 5 retained_intron

ENST00000303088, ENST00000392324, ENST00000407360, ENST00000421262, ENST00000456252, ENST00000535017, ENST00000536253, ENST00000540977, ENST00000540981, ENST00000541873, ENST00000543118, ENST00000543157, ENST00000544923, ENST00000545522, ENST00000593273, ENST00000892592, ENST00000892593, ENST00000892594, ENST00000892595, ENST00000892596, ENST00000892597, ENST00000892598, ENST00000926782, ENST00000926783, ENST00000926784, ENST00000943476, ENST00000943477, ENST00000943478, ENST00000943479, ENST00000943480

RefSeq mRNA: 10 — MANE Select: NM_003721 NM_001278727, NM_001278728, NM_001370233, NM_001370234, NM_001370235, NM_001370236, NM_001370237, NM_001370238, NM_003721, NM_134440

CCDS: CCDS12395, CCDS12396, CCDS62611

Canonical transcript exons

ENST00000303088 — 10 exons

Exon	Start	End
ENSE00001050094	19192960	19193100
ENSE00001113539	19198657	19198723
ENSE00003485682	19197186	19197251
ENSE00003486494	19193939	19194133
ENSE00003553275	19198107	19198232
ENSE00003645918	19196963	19197046
ENSE00003697001	19199154	19199234
ENSE00003697600	19192258	19192554
ENSE00003698717	19201649	19201866
ENSE00003789026	19197521	19197621

Expression profiles

Bgee: expression breadth ubiquitous, 270 present calls, max score 97.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.3350 / max 243.7495, expressed in 1819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174773	29.0368	1812
174772	3.9168	1447
174771	1.7979	1099
174774	0.5835	366

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.44	gold quality
mucosa of transverse colon	UBERON:0004991	97.28	gold quality
right uterine tube	UBERON:0001302	96.94	gold quality
right lobe of thyroid gland	UBERON:0001119	96.89	gold quality
ventricular zone	UBERON:0003053	96.82	gold quality
left lobe of thyroid gland	UBERON:0001120	96.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.45	gold quality
granulocyte	CL:0000094	96.20	gold quality
thyroid gland	UBERON:0002046	95.84	gold quality
endocervix	UBERON:0000458	95.71	gold quality
metanephros cortex	UBERON:0010533	95.46	gold quality
apex of heart	UBERON:0002098	95.24	gold quality
right ovary	UBERON:0002118	94.98	gold quality
left uterine tube	UBERON:0001303	94.96	gold quality
body of stomach	UBERON:0001161	94.94	gold quality
body of uterus	UBERON:0009853	94.89	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.85	gold quality
skin of abdomen	UBERON:0001416	94.79	gold quality
spleen	UBERON:0002106	94.79	gold quality
esophagus mucosa	UBERON:0002469	94.78	gold quality
ectocervix	UBERON:0012249	94.75	gold quality
adenohypophysis	UBERON:0002196	94.66	gold quality
left ovary	UBERON:0002119	94.56	gold quality
skin of leg	UBERON:0001511	94.46	gold quality
stromal cell of endometrium	CL:0002255	94.45	gold quality
transverse colon	UBERON:0001157	94.45	gold quality
omental fat pad	UBERON:0010414	94.44	gold quality
tibial nerve	UBERON:0001323	94.41	gold quality
peritoneum	UBERON:0002358	94.39	gold quality
minor salivary gland	UBERON:0001830	94.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.17

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

21 targets.

Target	Regulation
ANKRA2
ATP9A
CD74
CIITA
HLA-DMA	Unknown
HLA-DMB	Unknown
HLA-DOA	Unknown
HLA-DOB	Unknown
HLA-DPA1	Unknown
HLA-DPB1	Unknown
HLA-DQA1	Unknown
HLA-DQA2	Unknown
HLA-DQB1	Unknown
HLA-DQB2	Unknown
HLA-DRA	Unknown
HLA-DRB1	Unknown
HLA-DRB3	Unknown
HLA-DRB4	Unknown
HLA-DRB5	Unknown
HLA-E	Unknown
IFNG

JASPAR motifs

Motif	Name	Family
MA1554.1	RFX7	RFX-related factors
MA1554.2	RFX7	RFX-related factors

JASPAR matrix evidence (PMIDs): PMID:23354101

miRNA regulators (miRDB)

15 targeting RFXANK, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-642B-5P	96.37	67.26	745

Literature-anchored findings (GeneRIF, showing 12)

• Low levels of RFX-B are found in macrophages of colorectal cancer patients, partly explaining immunodeficiency in cancer. (PMID:11836625)
• in vivo effects of mutations on the expression of the RFXANK RNA and protein (PMID:12618906)
• ANKRA, RFXANK, and CIITA are novel targets of class IIa HDACs which may deacetylases play a role in regulating MHCII expression (PMID:15964851)
• analysis of RFXANK domains and function (PMID:16166641)
• RFXAP and RFXB have roles in relieving autoinhibition of RFX5 (PMID:18723135)
• Findings confirm the association between the high frequency of the combined immunodeficiency and the defect in MHC class II expression and provides strong evidence for a founder effect of the 752delG26 mutation in the North African population. (PMID:20414676)
• genetic, clinical, and immunologic features of 35 patients from 30 unrelated kindreds from North Africa sharing the same RFXANK founder mutation, a 26-bp deletion called I5E6-25_I5E6 + 1) (PMID:21908431)
• mutation results in Bare Lymphocyte Syndrome, Type 2 in a child of Mexican descent (PMID:26634365)
• these data identify a novel caspase-2-interacting factor, RFXANK, and indicate a potential non-apoptotic role for the enzyme in the control of MHC class II gene regulation. (PMID:29362422)
• this study reports an 8 month-old girl with MHC class II deficiency with a novel homozygous mutation in RFXANK gene and normal CD4+ T cell counts, diagnosed by whole exome sequencing and negative HLA-DR proteins on peripheral blood mononuclear cell in flow cytometry (PMID:30644704)
• Structural basis for the recognition of RFX7 by ANKRA2 and RFXANK. (PMID:31864703)
• Clinical, Immunological, and Genetic Findings in Iranian Patients with MHC-II Deficiency: Confirmation of c.162delG RFXANK Founder Mutation in the Iranian Population. (PMID:37584719)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rfxank	ENSDARG00000016730
mus_musculus	Rfxank	ENSMUSG00000036120
rattus_norvegicus	Rfxank	ENSRNOG00000033318

Paralogs (3): NFKBIZ (ENSG00000144802), ANKRA2 (ENSG00000164331), NFKBID (ENSG00000167604)

Protein

Protein identifiers

DNA-binding protein RFXANK — O14593 (reviewed: O14593)

Alternative names: Ankyrin repeat family A protein 1, Regulatory factor X subunit B, Regulatory factor X-associated ankyrin-containing protein

All UniProt accessions (8): O14593, A0A024R7P0, F5GY33, F5H7D2, H0YFU5, H0YFZ0, H0YGQ6, K7ENE6

UniProt curated annotations — full annotation on UniProt →

Function. Activates transcription from class II MHC promoters. Activation requires the activity of the MHC class II transactivator/CIITA. May regulate other genes in the cell. RFX binds the X1 box of MHC-II promoters. May also potentiate the activation of RAF1. Isoform 2 is not involved in the positive regulation of MHC class II genes.

Subunit / interactions. Forms homodimers. The RFX heterotetrameric complex consists of 2 molecules of RFX5 and one each of RFXAP and RFX-B/RFXANK; with each subunit representing a separate complementation group. Interacts (via ankyrin repeats) with RFX5 (via PxLPxI/L motif); the interaction is direct. RFX forms cooperative DNA binding complexes with X2BP and CBF/NF-Y. RFX associates with CIITA to form an active transcriptional complex. Interacts with RAF1. Interacts (via ankyrin repeats) with RFX7 (via PxLPxI/L motif).

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated by RAF1.

Disease relevance. MHC class II deficiency 2 (MHC2D2) [MIM:620815] An autosomal recessive disorder characterized by immunodeficiency and recurrent bacterial, viral, fungal and parasitic infections in early infancy. Additional manifestations include failure to thrive, chronic diarrhea, and autoimmune features and allergies that may be present in some patients. Death often occurs in infancy or early childhood. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Interacts with RAF1 via its C-terminal ankyrin repeat domain. The same domain also mediates its homodimerization. The third ankyrin repeat is required for association with the two other RFX subunits; RFX5 and RFXAP. The three central ANK repeats mediate binding to the PxLPxI/L motif of RFX5.

Isoforms (3)

UniProt ID	Names	Canonical?
O14593-1	1, Long	yes
O14593-2	2, RFX-B-delta5
O14593-3	3

RefSeq proteins (10): NP_001265656, NP_001265657, NP_001357162, NP_001357163, NP_001357164, NP_001357165, NP_001357166, NP_001357167, NP_003712, NP_604389 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR017362	DNA-bd_RFXANK	Family
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily

Pfam: PF00023, PF12796

UniProt features (32 total): helix 11, sequence variant 6, repeat 5, splice variant 3, mutagenesis site 2, compositionally biased region 2, chain 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3V30	X-RAY DIFFRACTION	1.57
6MEW	X-RAY DIFFRACTION	1.78
3UXG	X-RAY DIFFRACTION	1.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14593-F1	78.90	0.60

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
121	loss of expression.
224	loss of interaction with rfx5.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 250 (showing top): TGCGCANK_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, SANSOM_APC_TARGETS_DN, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, AACTTT_UNKNOWN, MARTIN_INTERACT_WITH_HDAC, CART1_01, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX, TAATTA_CHX10_01, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX

GO Biological Process (3): Ras protein signal transduction (GO:0007265), positive regulation of MHC class II biosynthetic process (GO:0045348), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (5): DNA binding (GO:0003677), histone deacetylase binding (GO:0042826), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), intercellular bridge (GO:0045171), RNA polymerase II transcription regulator complex (GO:0090575), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
small GTPase-mediated signal transduction	1
positive regulation of macromolecule biosynthetic process	1
MHC class II biosynthetic process	1
regulation of MHC class II biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
nucleic acid binding	1
enzyme binding	1
transcription cis-regulatory region binding	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
transcription regulator complex	1
nuclear protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFXANK	RFXAP	O00287	999
RFXANK	RFX5	P48382	999
RFXANK	CIITA	P33076	971
RFXANK	RFX1	P22670	954
RFXANK	CREB1	P16220	905
RFXANK	NFYC	Q13952	841
RFXANK	NFYA	P23511	819
RFXANK	MEF2B	Q02080	795
RFXANK	NCAN	O14594	742
RFXANK	NLRC5	Q86WI3	725
RFXANK	NFYB	P25208	698
RFXANK	HLA-DRA	P01903	683
RFXANK	RFX2	P48378	659
RFXANK	PRR19	A6NJB7	650
RFXANK	LRP2	P98164	631

IntAct

34 interactions, top by confidence:

A	B	Type	Score
RFX5	RFXAP	psi-mi:“MI:0914”(association)	0.880
RFXANK	RFX5	psi-mi:“MI:0407”(direct interaction)	0.850
RFX5	RFXANK	psi-mi:“MI:0915”(physical association)	0.850
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
RFXANK	RFXAP	psi-mi:“MI:0407”(direct interaction)	0.780
RFXANK	RFX7	psi-mi:“MI:0407”(direct interaction)	0.760
RFXANK	BLTP3B	psi-mi:“MI:0914”(association)	0.350
RAF1	EIF3F	psi-mi:“MI:0914”(association)	0.350
RAF1	ARID1A	psi-mi:“MI:0914”(association)	0.350
KLK15	DENND11	psi-mi:“MI:0914”(association)	0.350
NPAS1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
C18orf21	RFXANK	psi-mi:“MI:0914”(association)	0.350
HNF4A	TAF4	psi-mi:“MI:2364”(proximity)	0.270
NFIX	TAF4	psi-mi:“MI:2364”(proximity)	0.270
NFYC	ASDURF	psi-mi:“MI:2364”(proximity)	0.270
BSG	RFXANK	psi-mi:“MI:0915”(physical association)	0.000
NFKBIL1	RFXANK	psi-mi:“MI:0915”(physical association)	0.000
PHLDA3	RFXANK	psi-mi:“MI:0915”(physical association)	0.000
RFXANK		psi-mi:“MI:0915”(physical association)	0.000
RFXANK	DCTN1	psi-mi:“MI:0915”(physical association)	0.000
RFXANK	TBR1	psi-mi:“MI:0915”(physical association)	0.000
RFXANK	DDOST	psi-mi:“MI:0915”(physical association)	0.000
RAB5IF	RFXANK	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (169): RFXANK (Affinity Capture-RNA), RFXANK (Affinity Capture-RNA), RFXANK (Affinity Capture-RNA), RFX5 (Affinity Capture-MS), RFX7 (Affinity Capture-MS), LMNB2 (Affinity Capture-MS), SOGA1 (Affinity Capture-MS), HUWE1 (Affinity Capture-MS), LMNA (Affinity Capture-MS), BAG6 (Affinity Capture-MS), RFXAP (Affinity Capture-MS), PHB2 (Affinity Capture-MS), UHRF1BP1 (Affinity Capture-MS), ARHGEF11 (Affinity Capture-MS), UBL4A (Affinity Capture-MS)

ESM2 similar proteins: A2AQW0, A5PMU4, A6NFN9, A6NK59, B4E2M5, E1C3P4, H2LP95, O14593, O94967, P0C927, P15056, P34908, P59672, Q28FJ2, Q2KI79, Q3SX45, Q3UMR0, Q3V096, Q5REW9, Q5SUE8, Q5TZF3, Q5U2S6, Q640N2, Q641K1, Q66H07, Q69ZK0, Q6AI12, Q6ZN16, Q810N6, Q8BIZ1, Q8C0W1, Q8C6Y6, Q8CGF6, Q8K0L0, Q8N9B4, Q8TCU6, Q8VDD9, Q92625, Q96NW4, Q96Q27

Diamond homologs: A0A084B9Z8, A2AS55, A4II29, A6NGH8, B4E2M5, F1MJR8, O14593, O75762, Q337A0, Q3KP44, Q3SX00, Q3V096, Q499M5, Q4UMP3, Q54HW1, Q5R8C8, Q5RCK5, Q5U5A6, Q5ZLC8, Q6RI86, Q7T3X9, Q7T3Y0, Q7Z6K4, Q86W74, Q86WC6, Q875S9, Q876L4, Q8BLA8, Q8BLD6, Q8BTI7, Q8C0T1, Q8IWB6, Q91ZA8, Q91ZU0, Q96KQ7, Q9BGT9, Q9BZL4, Q9D119, Q9H672, Q9JRZ6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RFXANK	“form complex”	“RFX complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	12
Uncertain significance	103
Likely benign	140
Benign	5

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1072999	NM_003721.4(RFXANK):c.383del (p.Leu128fs)	Pathogenic
1074711	NM_003721.4(RFXANK):c.634C>T (p.Arg212Ter)	Pathogenic
1361889	NM_003721.4(RFXANK):c.599_600del (p.Gly200fs)	Pathogenic
1366008	NM_003721.4(RFXANK):c.532G>T (p.Glu178Ter)	Pathogenic
1435455	NM_003721.4(RFXANK):c.338-25_338del	Pathogenic
2152313	NM_003721.4(RFXANK):c.600del (p.Asn201fs)	Pathogenic
2424745	NC_000019.9:g.(?19304756)(19304962_?)del	Pathogenic
3236742	NM_003721.4(RFXANK):c.163del (p.Asp55fs)	Pathogenic
3629746	NM_003721.4(RFXANK):c.563G>A (p.Trp188Ter)	Pathogenic
4279080	NM_003721.4(RFXANK):c.469C>T (p.Arg157Ter)	Pathogenic
4711935	NM_003721.4(RFXANK):c.240dup (p.Glu81fs)	Pathogenic
4735652	NM_003721.4(RFXANK):c.438G>A (p.Trp146Ter)	Pathogenic
573785	NM_003721.4(RFXANK):c.271_271+1insCTGCC	Pathogenic
992971	NM_003721.4(RFXANK):c.271+1delinsTCAC	Pathogenic
1067781	NM_003721.4(RFXANK):c.337+2_337+3del	Likely pathogenic
1504417	NM_003721.4(RFXANK):c.188-2del	Likely pathogenic
191297	Single allele	Likely pathogenic
2501290	NM_003721.4(RFXANK):c.564+2T>C	Likely pathogenic
2634018	NM_003721.4(RFXANK):c.194_198del (p.Ser65fs)	Likely pathogenic
3362569	NM_003721.4(RFXANK):c.8_11del (p.Leu3fs)	Likely pathogenic
3583548	NM_003721.4(RFXANK):c.140del (p.Pro47fs)	Likely pathogenic
3583549	NM_003721.4(RFXANK):c.272-2A>C	Likely pathogenic
4086147	NM_003721.4(RFXANK):c.34C>T (p.Gln12Ter)	Likely pathogenic
643059	NM_003721.4(RFXANK):c.419_438+38del	Likely pathogenic
827735	NM_003721.4(RFXANK):c.584T>C (p.Leu195Pro)	Likely pathogenic
976235	NM_003721.4(RFXANK):c.460del (p.Ala154fs)	Likely pathogenic

SpliceAI

1977 predictions. Top by Δscore:

Variant	Effect	Δscore
19:19192087:T:TA	donor_gain	1.0000
19:19192088:C:A	donor_gain	1.0000
19:19192503:ATAAG:A	donor_gain	1.0000
19:19193924:T:A	acceptor_gain	1.0000
19:19193928:A:AG	acceptor_gain	1.0000
19:19193929:C:G	acceptor_gain	1.0000
19:19193933:C:CA	acceptor_gain	1.0000
19:19193938:GCT:G	acceptor_gain	1.0000
19:19194060:G:GA	donor_gain	1.0000
19:19194132:GG:G	donor_gain	1.0000
19:19194133:GG:G	donor_gain	1.0000
19:19194134:G:T	donor_gain	1.0000
19:19196961:A:AG	acceptor_gain	1.0000
19:19196962:G:GG	acceptor_gain	1.0000
19:19196962:GCA:G	acceptor_gain	1.0000
19:19196963:CAG:C	acceptor_loss	1.0000
19:19196964:A:AG	acceptor_gain	1.0000
19:19196964:AGG:A	acceptor_loss	1.0000
19:19196965:G:GG	acceptor_gain	1.0000
19:19196965:GGCA:G	acceptor_gain	1.0000
19:19197042:AGACT:A	donor_gain	1.0000
19:19197043:GACT:G	donor_gain	1.0000
19:19197043:GACTG:G	donor_gain	1.0000
19:19197044:ACT:A	donor_gain	1.0000
19:19197044:ACTG:A	donor_loss	1.0000
19:19197045:CT:C	donor_gain	1.0000
19:19197045:CTGTG:C	donor_loss	1.0000
19:19197046:TGTG:T	donor_loss	1.0000
19:19197047:G:GG	donor_gain	1.0000
19:19197047:GTGA:G	donor_loss	1.0000

AlphaMissense

1667 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:19197587:G:T	G135V	1.000
19:19198161:A:C	S165R	1.000
19:19198163:C:A	S165R	1.000
19:19198163:C:G	S165R	1.000
19:19198707:C:G	C205W	1.000
19:19199208:T:C	L229P	1.000
19:19197231:T:C	L106P	0.999
19:19197556:T:C	F125L	0.999
19:19197558:C:A	F125L	0.999
19:19197558:C:G	F125L	0.999
19:19197566:T:A	L128H	0.999
19:19197566:T:C	L128P	0.999
19:19197574:G:C	A131P	0.999
19:19197575:C:A	A131D	0.999
19:19197578:C:A	S132Y	0.999
19:19197611:T:C	L143P	0.999
19:19197614:T:C	L144P	0.999
19:19198143:A:C	S159R	0.999
19:19198145:C:A	S159R	0.999
19:19198145:C:G	S159R	0.999
19:19198156:T:C	L163P	0.999
19:19198159:C:A	A164D	0.999
19:19198171:G:T	G168V	0.999
19:19198195:T:C	L176P	0.999
19:19198228:A:T	D187V	0.999
19:19198670:C:A	P193Q	0.999
19:19198670:C:G	P193R	0.999
19:19198673:T:C	L194P	0.999
19:19198681:G:C	A197P	0.999
19:19198682:C:A	A197D	0.999

dbSNP variants (sampled 300 via entrez): RS1000197189 (19:19200168 G>A,T), RS1000416942 (19:19190486 C>T), RS1000488766 (19:19200796 T>A,C), RS1000683797 (19:19200588 A>G), RS1000737490 (19:19196011 G>A), RS1000845176 (19:19194340 C>A,T), RS1001091270 (19:19195687 G>A), RS1001368041 (19:19201045 C>A,T), RS1001404782 (19:19195805 G>A), RS1001910748 (19:19196366 C>T), RS1002023757 (19:19191105 C>T), RS1002417973 (19:19200476 G>A,C), RS1002738410 (19:19193371 C>A,T), RS1002811536 (19:19193792 C>G), RS1003051856 (19:19193073 C>T)

Disease associations

OMIM: gene MIM:603200 | disease phenotypes: MIM:209920, MIM:620815, MIM:620818, MIM:620816

GenCC curated gene-disease

Disease	Classification	Inheritance
MHC class II deficiency	Strong	Autosomal recessive
MHC class II deficiency 2	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
MHC class II deficiency	Definitive	AR

Mondo (5): MHC class II deficiency (MONDO:0008855), MHC class II deficiency 2 (MONDO:0971013), MHC class II deficiency 1 (MONDO:0971005), MHC class II deficiency 5 (MONDO:0971016), MHC class II deficiency 3 (MONDO:0971014)

Orphanet (1): Immunodeficiency by defective expression of MHC class II (Orphanet:572)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000246	Sinusitis
HP:0000371	Acute otitis media
HP:0000988	Skin rash
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001508	Failure to thrive
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001890	Autoimmune hemolytic anemia
HP:0001904	Autoimmune neutropenia
HP:0001973	Autoimmune thrombocytopenia
HP:0001999	Abnormal facial shape
HP:0002014	Diarrhea
HP:0002028	Chronic diarrhea
HP:0002061	Lower limb spasticity
HP:0002066	Gait ataxia
HP:0002205	Recurrent respiratory infections
HP:0002240	Hepatomegaly
HP:0002718	Recurrent bacterial infections
HP:0002726	Recurrent Staphylococcus aureus infections
HP:0002728	Chronic mucocutaneous candidiasis
HP:0002783	Recurrent lower respiratory tract infections
HP:0002788	Recurrent upper respiratory tract infections
HP:0002841	Recurrent fungal infections
HP:0002960	Autoimmunity
HP:0003139	Panhypogammaglobulinemia
HP:0003593	Infantile onset
HP:0004313	Decreased circulating immunoglobulin concentration

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST008103_10	Bipolar disorder	1.000000e-09
GCST008115_2	Bipolar I disorder	3.000000e-09
GCST008116_4	Bipolar II disorder	4.000000e-06
GCST010002_52	Refractive error	4.000000e-29

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009963	bipolar I disorder
EFO:0009964	bipolar II disorder

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537079	Bare lymphocyte syndrome 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Sarin	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Paclitaxel	affects response to substance	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	decreases expression	1
Chlorodiphenyl (54% Chlorine)	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

Cellosaurus cell lines

8 cell lines: 8 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_9W20	BLS-1	Transformed cell line	Male
CVCL_9W22	BLS-1.DR4	Transformed cell line	Male
CVCL_9W23	BLS-1.DR5	Transformed cell line	Male
CVCL_B7K3	EBA	Transformed cell line	Male
CVCL_B7K4	FZA	Transformed cell line	Male
CVCL_B7K5	Bequit	Transformed cell line	Male
CVCL_B7K6	Nacera	Transformed cell line	Female
CVCL_B7K7	Ramia	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01652092	Not specified	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies
NCT04251325	Not specified	UNKNOWN	Socio-demographic Characteristics of Basic Life Support Course Participants
NCT04353089	Not specified	UNKNOWN	Geographical Association Between Basic Life Support Courses, Bystander Cardiopulmonary Resuscitation and Survival