CRACR2A

Summary

CRACR2A (calcium release activated channel regulator 2A, HGNC:28657) is a protein-coding gene on chromosome 12p13.32, encoding EF-hand calcium-binding domain-containing protein 4B (Q9BSW2). Ca(2+)-binding protein that plays a key role in store-operated Ca(2+) entry (SOCE) in T-cells by regulating CRAC channel activation.

Enables GTPase activity and calcium ion binding activity. Involved in several processes, including activation of store-operated calcium channel activity; positive regulation of JNK cascade; and store-operated calcium entry. Located in several cellular components, including Golgi apparatus; Weibel-Palade body; and immunological synapse.

Source: NCBI Gene 84766 — RefSeq curated summary.

At a glance

• Gene–disease (curated): combined immunodeficiency (Limited, ClinGen)
• GWAS associations: 8
• Clinical variants (ClinVar): 159 total — 1 pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_001144958

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28657
Approved symbol	CRACR2A
Name	calcium release activated channel regulator 2A
Location	12p13.32
Locus type	gene with protein product
Status	Approved
Aliases	MGC4266, RAB46
Ensembl gene	ENSG00000130038
Ensembl biotype	protein_coding
OMIM	614178
Entrez	84766

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000252322, ENST00000333750, ENST00000440314, ENST00000514026, ENST00000535292, ENST00000535507, ENST00000893446, ENST00000893447, ENST00000893448, ENST00000944630, ENST00000944631, ENST00000944632, ENST00000944633

RefSeq mRNA: 2 — MANE Select: NM_001144958 NM_001144958, NM_032680

CCDS: CCDS44803, CCDS8522

Canonical transcript exons

ENST00000440314 — 20 exons

Exon	Start	End
ENSE00001366638	3732942	3733210
ENSE00001371869	3713237	3713317
ENSE00001631456	3615328	3615439
ENSE00001649455	3654212	3654399
ENSE00001683288	3656311	3656406
ENSE00001685207	3678915	3679098
ENSE00001710471	3673446	3673592
ENSE00001744975	3680238	3680349
ENSE00001746411	3638124	3638454
ENSE00001750198	3659564	3659654
ENSE00001764797	3648542	3648613
ENSE00002214377	3753015	3753109
ENSE00002260533	3696772	3697035
ENSE00003472836	3627625	3627706
ENSE00003474880	3619271	3619372
ENSE00003499076	3627436	3627550
ENSE00003529690	3644595	3644640
ENSE00003649080	3641732	3641838
ENSE00003678552	3616954	3617030
ENSE00003681013	3633604	3633736

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 97.54.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8524 / max 193.3725, expressed in 852 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128994	1.9841	627
128995	0.5029	265
128996	0.1774	77
128997	0.1515	53
128992	0.0365	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	97.54	gold quality
ileal mucosa	UBERON:0000331	96.07	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.12	gold quality
nasal cavity epithelium	UBERON:0005384	93.45	gold quality
colonic mucosa	UBERON:0000317	91.97	gold quality
nasal cavity mucosa	UBERON:0001826	91.54	gold quality
saliva-secreting gland	UBERON:0001044	88.45	gold quality
rectum	UBERON:0001052	88.44	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.28	gold quality
trachea	UBERON:0003126	87.00	gold quality
minor salivary gland	UBERON:0001830	86.09	gold quality
bone marrow cell	CL:0002092	85.85	gold quality
bronchial epithelial cell	CL:0002328	85.41	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.40	gold quality
bronchus	UBERON:0002185	85.08	gold quality
pancreatic ductal cell	CL:0002079	84.86	silver quality
colonic epithelium	UBERON:0000397	84.56	gold quality
epithelium of nasopharynx	UBERON:0001951	84.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.22	gold quality
mucosa of transverse colon	UBERON:0004991	83.01	gold quality
granulocyte	CL:0000094	82.74	gold quality
mouth mucosa	UBERON:0003729	82.69	gold quality
thymus	UBERON:0002370	82.48	gold quality
palpebral conjunctiva	UBERON:0001812	81.74	gold quality
tonsil	UBERON:0002372	81.49	gold quality
blood	UBERON:0000178	81.44	gold quality
upper leg skin	UBERON:0004262	81.11	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.86	gold quality
amniotic fluid	UBERON:0000173	80.52	gold quality
small intestine	UBERON:0002108	80.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.40
E-MTAB-7606	no	1080.02
E-GEOD-100618	no	436.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting CRACR2A, 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-4803	99.98	71.99	3117
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-628-5P	98.36	67.74	844
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-1910-5P	97.42	66.36	844
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-874-5P	96.93	63.92	1014
HSA-MIR-3126-5P	96.87	65.83	912
HSA-MIR-6875-5P	96.87	65.49	958
HSA-MIR-3907	96.76	65.04	662

Literature-anchored findings (GeneRIF, showing 7)

• CRACR2A interacts directly with Orai1 and STIM1, forming a ternary complex that dissociates at elevated Ca(2+) concentrations; is a key regulator of CRAC channel-mediated SOCE (PMID:20418871)
• endothelial cells contain a long variant of CRACR2A which is an EF-hand-containing Rab protein that lacks impact on CRAC channels (PMID:25475730)
• GTP binding and prenylation of CRACR2A were associated with its localization near the Golgi and its stability (PMID:27016526)
• Results show the characterization of CRACR2A protein which encodes a large Rab GTPase containing multiple functional domains contrary to small Rab GTPases. It was found to play an unexpected role in regulating intracellular signaling pathways important for T cell activation. (PMID:27221160)
• There is a significant association between the EFCAB4B gene and localized periodontitis. (PMID:30284742)
• Vigorous physical activity before diagnosis is associated with epigenetic alterations of CRACR2A and prostate cancer metastatic-lethal progression. (PMID:30464020)
• These data demonstrate for the first time that a Rab GTPase, Rab46, integrates G protein and Ca(2+) signals to couple on-demand histamine signals to selective Weibel-Palade bodies (WPBs) trafficking. (PMID:31092558)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cracr2ab	ENSDARG00000045758
danio_rerio	CRACR2A	ENSDARG00000068231
mus_musculus	Cracr2a	ENSMUSG00000061414
rattus_norvegicus	Cracr2a	ENSRNOG00000053449

Paralogs (1): CRACR2B (ENSG00000177685)

Protein

Protein identifiers

EF-hand calcium-binding domain-containing protein 4B — Q9BSW2 (reviewed: Q9BSW2)

Alternative names: Calcium release-activated calcium channel regulator 2A, Calcium release-activated channel regulator 2A, Ras-related protein Rab-46

All UniProt accessions (3): Q9BSW2, H0YFI5, H7BXT2

UniProt curated annotations — full annotation on UniProt →

Function. Ca(2+)-binding protein that plays a key role in store-operated Ca(2+) entry (SOCE) in T-cells by regulating CRAC channel activation. Acts as a cytoplasmic calcium-sensor that facilitates the clustering of ORAI1 and STIM1 at the junctional regions between the plasma membrane and the endoplasmic reticulum upon low Ca(2+) concentration. It thereby regulates CRAC channel activation, including translocation and clustering of ORAI1 and STIM1. Upon increase of cytoplasmic Ca(2+) resulting from opening of CRAC channels, dissociates from ORAI1 and STIM1, thereby destabilizing the ORAI1-STIM1 complex. Rab GTPase that mediates the trafficking of Weibel-Palade bodies (WPBs) to microtubule organizing center (MTOC) in endothelial cells in response to acute inflammatory stimuli. During histamine (but not thrombin) stimulation of endothelial cells, the dynein-bound form induces retrograde transport of a subset of WPBs along microtubules to the MTOC in a Ca(2+)-independent manner and its GTPase activity is essential for this function. Ca(2+)-regulated dynein adapter protein that activates dynein-mediated transport and dynein-dynactin motility on microtubules and regulates endosomal trafficking of CD47. Acts as an intracellular signaling module bridging two important T-cell receptor (TCR) signaling pathways, Ca(2+)-NFAT and JNK, to affect T-cell activation. In resting T-cells, is predominantly localized near TGN network in a GTP-bound form, upon TCR stimulation, localizes at the immunological synapse via interaction with VAV1 to activate downstream Ca(2+)-NFAT and JNK signaling pathways. Plays a role in T-helper 1 (Th1) cell differentiation and T-helper 17 (Th17) cell effector function. Plays a role in store-operated Ca(2+) entry (SOCE) in T-cells by regulating CRAC channel activation.

Subunit / interactions. Interacts with ORAI1 and STIM1; the interaction is direct and takes place in absence of Ca(2+). Forms a complex with ORAI1 and STIM1 at low concentration of Ca(2+), the complex dissociates at elevated Ca(2+) concentrations. Interacts with ORAI2 and ORAI3. Interacts with DYNC1H1. Interacts with the dynein-dynactin complex in a Ca(2+)-dependent manner. Interacts with VAV1.

Subcellular location. Cytoplasm Cytoplasm. Cytoplasm. Cytoskeleton. Microtubule organizing center. Cell membrane. Golgi apparatus membrane. Golgi apparatus. trans-Golgi network membrane. Vesicle.

Tissue specificity. Expressed in the Jurkat T-cell line. Expressed in endothelial cells. Expressed in Weibel-Palade bodies (which are P-selectin/SELP negative) in endothelial cells. Expressed in the Jurkat T-cell line.

Similarity. Belongs to the EFCAB4 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BSW2-2	2, CRACR2A-L, CRACR2A-A	yes
Q9BSW2-1	1, CRACR2A-S, CRACR2A-C

RefSeq proteins (2): NP_001138430, NP_116069 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001806	Small_GTPase	Family
IPR002048	EF_hand_dom	Domain
IPR005225	Small_GTP-bd	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR050227	Rab	Family

Pfam: PF00071, PF13499

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = GDP + phosphate + H(+) (RHEA:19669)

UniProt features (58 total): binding site 22, mutagenesis site 9, region of interest 6, sequence variant 6, helix 5, strand 3, splice variant 2, chain 1, domain 1, lipid moiety-binding region 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6PSD	X-RAY DIFFRACTION	2.66

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSW2-F1	70.34	0.36

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 (22): 99; 101; 103; 108; 554; 556; 557; 558; 559; 559; 560; 571 …

Post-translational modifications (1): 729

Mutagenesis-validated functional residues (9):

Position	Phenotype
63	loss of calcium-binding and interaction with the dynein-dynactin complex; when associated with a-65; a-97 and a-99.
65	loss of calcium-binding and interaction with the dynein-dynactin complex; when associated with a-63; a-97 and a-99.
97–99	in ef2mut; enhanced stim1 clustering and elevated cytoplasmic ca2+, thereby causing cell death in t-cells. loss of calci
97	loss of calcium-binding and interaction with the dynein-dynactin complex; when associated with a-63; a-65 and a-99.
99	loss of calcium-binding and interaction with the dynein-dynactin complex; when associated with a-63; a-65 and a-97.
559	gdp-binding mutant with reduced gtpase activity and protein stability. reduced ability to activate jnk signaling pathway
604	gtp-binding mutant with reduced gtpase activity but increased protein stability. increased ability to activate jnk signa
658	gtp/gdp-binding defective mutant with reduced gtpase activity and protein stability. failure to localize to the microtub
729–731	failure to localize to the golgi membrane.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 118 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_CATION_CHANNEL_ACTIVITY, GOCC_SECRETORY_GRANULE, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_TRANSPORTER_ACTIVITY, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOZGIT_ESR1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_VESICLE_MEDIATED_TRANSPORT, CAGCTG_AP4_Q5, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOCC_MICROTUBULE_ORGANIZING_CENTER

GO Biological Process (13): store-operated calcium entry (GO:0002115), adaptive immune response (GO:0002250), intracellular protein localization (GO:0008104), vesicle-mediated transport (GO:0016192), endosomal transport (GO:0016197), activation of store-operated calcium channel activity (GO:0032237), response to histamine (GO:0034776), T-helper 1 cell differentiation (GO:0045063), positive regulation of JNK cascade (GO:0046330), positive regulation of calcium ion transport (GO:0051928), immune system process (GO:0002376), monoatomic ion transport (GO:0006811), calcium ion transport (GO:0006816)

GO Molecular Function (8): GTPase activity (GO:0003924), G protein activity (GO:0003925), calcium ion binding (GO:0005509), GTP binding (GO:0005525), nucleotide binding (GO:0000166), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (14): Golgi membrane (GO:0000139), immunological synapse (GO:0001772), extracellular region (GO:0005576), cytoplasm (GO:0005737), microtubule organizing center (GO:0005815), plasma membrane (GO:0005886), membrane (GO:0016020), vesicle (GO:0031982), trans-Golgi network membrane (GO:0032588), Weibel-Palade body (GO:0033093), specific granule lumen (GO:0035580), Golgi apparatus (GO:0005794), cytoskeleton (GO:0005856), specific granule (GO:0042581)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
calcium ion transport	2
transport	2
secretory granule	2
immune response	1
macromolecule localization	1
cellular process	1
vesicle-mediated transport	1
intracellular transport	1
positive regulation of store-operated calcium channel activity	1
response to nitrogen compound	1
alpha-beta T cell activation involved in immune response	1
T cell differentiation involved in immune response	1
T-helper 1 type immune response	1
T-helper cell differentiation	1
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
positive regulation of monoatomic ion transport	1
regulation of calcium ion transport	1
biological_process	1
metal ion transport	1
ribonucleoside triphosphate phosphatase activity	1
GTPase activity	1
molecular function regulator activity	1
metal ion binding	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
plasma membrane	1
intracellular anatomical structure	1
microtubule cytoskeleton	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

818 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRACR2A	STIM1	Q13586	922
CRACR2A	ORAI1	Q96D31	766
CRACR2A	SARAF	Q96BY9	745
CRACR2A	STIMATE	Q86TL2	698
CRACR2A	EFHB	Q8N7U6	619
CRACR2A	C11orf97	A0A1B0GVM6	583
CRACR2A	STIM2	Q9P246	558
CRACR2A	CALM1	P02593	530
CRACR2A	BICDL1	Q6ZP65	490
CRACR2A	ORAI2	Q96SN7	482
CRACR2A	SLC35G1	Q2M3R5	480
CRACR2A	BICDL2	A1A5D9	466
CRACR2A	RAB11FIP3	O75154	457
CRACR2A	ORAI3	Q9BRQ5	456
CRACR2A	ASPH	Q12797	447

IntAct

158 interactions, top by confidence:

A	B	Type	Score
ORAI1	STIM1	psi-mi:“MI:0914”(association)	0.960
TLE5	CRACR2A	psi-mi:“MI:0915”(physical association)	0.670
CRACR2A	TLE5	psi-mi:“MI:0915”(physical association)	0.670
CLUAP1	CRACR2A	psi-mi:“MI:0915”(physical association)	0.590
ORAI1	CRACR2A	psi-mi:“MI:0407”(direct interaction)	0.590
CRACR2A	ORAI1	psi-mi:“MI:0407”(direct interaction)	0.590
ORAI1	CRACR2A	psi-mi:“MI:0915”(physical association)	0.590
CRACR2A	Hoxa1	psi-mi:“MI:0915”(physical association)	0.570
MKRN3	CRACR2A	psi-mi:“MI:0915”(physical association)	0.560
CRACR2A	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
CDC23	CRACR2A	psi-mi:“MI:0915”(physical association)	0.560
CRACR2A	MKRN3	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLA	CRACR2A	psi-mi:“MI:0915”(physical association)	0.560
CRACR2A	LRIF1	psi-mi:“MI:0915”(physical association)	0.560
CRACR2A	SLAIN1	psi-mi:“MI:0915”(physical association)	0.560
TRAF1	CRACR2A	psi-mi:“MI:0915”(physical association)	0.560
SORBS3	CRACR2A	psi-mi:“MI:0915”(physical association)	0.560
DDIT3	CRACR2A	psi-mi:“MI:0915”(physical association)	0.560
KRT75	CRACR2A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (82): CRACR2A (Two-hybrid), CRACR2A (Two-hybrid), CRACR2A (Two-hybrid), NOTCH2NL (Two-hybrid), CRACR2A (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), MCPH1 (Affinity Capture-MS), CRACR2A (Two-hybrid), CRACR2A (PCA), Hoxa1 (Affinity Capture-Western), CRACR2A (Affinity Capture-MS), CRACR2A (Affinity Capture-MS), MCPH1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), CRACR2A (Two-hybrid)

ESM2 similar proteins: A0JMQ7, A0JP75, A1A600, A2BGP7, B1A193, B1WBU8, B2RPU2, G9G127, H2MTR9, O88869, Q0VFN8, Q2TAA8, Q32LC2, Q3ULW6, Q3UP38, Q4R7V1, Q4V7B0, Q5EB20, Q5JU67, Q5PQQ9, Q5RDE3, Q5U4W1, Q5XIR4, Q61043, Q6AXZ4, Q6IP02, Q6IQY5, Q6IRU7, Q6NRK1, Q6NRX3, Q6PA69, Q6ZQ12, Q7Z3E5, Q86YF9, Q86YS3, Q8BIJ7, Q8BQP8, Q8CGZ2, Q8CJ96, Q8K342

Diamond homologs: A0JP75, A1A600, B0BNK9, Q3UP38, Q7Z6P3, Q80ZJ8, Q8CB87, Q8N4Y2, Q9BSW2, Q619T5, A4FV54, A5WW21, C4YL11, F1PTE3, O24466, O42819, P07560, P0CY30, P0CY31, P10536, P11620, P16976, P17609, P17610, P20790, P20791, P22125, P22127, P22128, P24409, P28186, P28187, P28188, P31584, P33723, P34139, P34140, P35280, P35286, P36861

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	119
Likely benign	9
Benign	19

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1047901	GRCh37/hg19 12p13.32(chr12:3619010-5221363)	Pathogenic

SpliceAI

4741 predictions. Top by Δscore:

Variant	Effect	Δscore
12:3615439:CCT:C	acceptor_loss	1.0000
12:3615440:C:CC	acceptor_gain	1.0000
12:3615441:T:G	acceptor_loss	1.0000
12:3617029:TCC:T	acceptor_loss	1.0000
12:3617031:C:CC	acceptor_gain	1.0000
12:3617031:C:G	acceptor_loss	1.0000
12:3617032:T:C	acceptor_loss	1.0000
12:3619222:C:A	donor_gain	1.0000
12:3619371:TCCTG:T	acceptor_loss	1.0000
12:3619373:C:CG	acceptor_loss	1.0000
12:3619374:T:A	acceptor_loss	1.0000
12:3627430:GCTCA:G	donor_loss	1.0000
12:3627431:CTCA:C	donor_loss	1.0000
12:3627432:TCA:T	donor_loss	1.0000
12:3627433:CACCT:C	donor_loss	1.0000
12:3627434:A:C	donor_loss	1.0000
12:3654205:GACTC:G	donor_loss	1.0000
12:3654206:ACTCA:A	donor_loss	1.0000
12:3654207:C:CG	donor_loss	1.0000
12:3654208:TCACA:T	donor_loss	1.0000
12:3654209:CAC:C	donor_loss	1.0000
12:3654210:A:AC	donor_gain	1.0000
12:3654210:A:AG	donor_loss	1.0000
12:3654211:C:CA	donor_gain	1.0000
12:3654211:CAT:C	donor_gain	1.0000
12:3654211:CATCT:C	donor_gain	1.0000
12:3654212:ATCT:A	donor_gain	1.0000
12:3654215:T:TA	donor_gain	1.0000
12:3654395:TCCAG:T	acceptor_gain	1.0000
12:3654396:CCAG:C	acceptor_gain	1.0000

AlphaMissense

4825 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:3617001:G:C	S688R	0.993
12:3617001:G:T	S688R	0.993
12:3617003:T:G	S688R	0.993
12:3680299:A:C	F93L	0.993
12:3680299:A:T	F93L	0.993
12:3680301:A:G	F93L	0.993
12:3627643:T:G	D600A	0.992
12:3627647:A:G	W599R	0.991
12:3627647:A:T	W599R	0.991
12:3627495:A:C	Y625D	0.989
12:3627644:C:G	D600H	0.989
12:3627643:T:A	D600V	0.988
12:3680251:G:C	F109L	0.988
12:3680251:G:T	F109L	0.988
12:3680253:A:G	F109L	0.988
12:3633666:T:A	K558M	0.987
12:3633685:C:G	G552R	0.987
12:3680252:A:G	F109S	0.987
12:3633669:C:T	G557E	0.986
12:3633684:C:A	G552V	0.986
12:3680267:A:G	L104P	0.986
12:3619328:C:A	K659N	0.985
12:3619328:C:G	K659N	0.985
12:3619331:A:C	N658K	0.985
12:3619331:A:T	N658K	0.985
12:3627642:G:C	D600E	0.985
12:3627642:G:T	D600E	0.985
12:3633667:T:G	K558Q	0.985
12:3633669:C:A	G557V	0.985
12:3627453:A:G	W639R	0.984

dbSNP variants (sampled 300 via entrez): RS1000029054 (12:3732915 C>A,G,T), RS1000033142 (12:3743243 T>A), RS1000070178 (12:3725178 C>T), RS1000107562 (12:3744429 T>A), RS1000169471 (12:3638956 G>A), RS1000185441 (12:3720042 C>T), RS1000194428 (12:3697811 T>A), RS1000221973 (12:3723475 C>T), RS1000232502 (12:3679707 G>A,T), RS1000271139 (12:3710680 C>A,T), RS1000285487 (12:3636608 A>C), RS1000294996 (12:3645282 G>A,C), RS1000299566 (12:3632690 C>A,G), RS1000393544 (12:3685842 G>A), RS1000422729 (12:3713798 G>A)

Disease associations

OMIM: gene MIM:614178 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
combined immunodeficiency	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
combined immunodeficiency	Limited	AR

Mondo (2): microcephaly (MONDO:0001149), combined immunodeficiency (MONDO:0015131)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000252	Microcephaly

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000412_4	Male infertility	4.000000e-06
GCST000766_9	Non-alcoholic fatty liver disease histology (lobular)	8.000000e-07
GCST001272_5	Cytomegalovirus antibody response	5.000000e-06
GCST002248_9	Fasting insulin (dietary factor interaction)	8.000000e-06
GCST002253_1	Homeostasis model assessment of insulin resistance (dietary factor interaction)	9.000000e-06
GCST007197_1	Chronic periodontitis (localised)	2.000000e-08
GCST012490_378	Femur bone mineral density x serum urate levels interaction	3.000000e-08
GCST90026413_2	Severe insulin-deficient type 2 diabetes	4.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0004501	HOMA-IR
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3638353 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

56 measured of 56 human assays (56 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-3-fluoropyridine-4-carboxamide	IC50	20.4 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-fluorophenyl]-5-methyl-1,2-oxazole-4-carboxamide	IC50	20.8 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[6-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-pyridinyl]-2-methylbenzamide	IC50	23 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-fluorophenyl]-2,3-difluorobenzamide	IC50	32.6 nM	US-8921364: Modulators of calcium release-activated calcium channel
4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-N-(4-methyl-1,3-thiazol-5-yl)benzamide	IC50	34.1 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-fluorophenyl]-4-methylthiadiazole-5-carboxamide	IC50	35.7 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-(3,5-dicyclopropylpyrazol-1-yl)phenyl]-2-methylbenzamide	IC50	36.4 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[6-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-pyridinyl]-3-fluoropyridine-4-carboxamide	IC50	37.6 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[6-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-pyridinyl]pyridine-3-carboxamide	IC50	47.2 nM	US-8921364: Modulators of calcium release-activated calcium channel
4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-N-[(4-methyl-1,3-thiazol-5-yl)methyl]aniline	IC50	48 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-fluorophenyl]-4-methyl-1,3-thiazole-5-carboxamide	IC50	48.2 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-2-pyridin-3-ylacetamide	IC50	48.2 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[6-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-pyridinyl]-2,6-difluorobenzamide	IC50	50.6 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-(difluoromethyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-4-methyl-1,3-thiazole-5-carboxamide	IC50	52.6 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[6-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-pyridinyl]-2-fluorobenzamide	IC50	60 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-(3,5-dicyclopropylpyrazol-1-yl)-3-fluorophenyl]-4-methylthiadiazole-5-carboxamide	IC50	60.3 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-(3,5-dicyclopropylpyrazol-1-yl)phenyl]-4-methylthiadiazole-5-carboxamide	IC50	62.4 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[6-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-pyridinyl]pyridine-4-carboxamide	IC50	62.6 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-5-methyl-1,2-oxazole-4-carboxamide	IC50	63.2 nM	US-8921364: Modulators of calcium release-activated calcium channel
3,5-dichloro-N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]pyridine-4-carboxamide	IC50	65.5 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[6-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-pyridinyl]-2,3-difluorobenzamide	IC50	70.3 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-4-methyl-1,3-thiazole-5-carboxamide	IC50	72 nM	US-8921364: Modulators of calcium release-activated calcium channel
6-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-N-(2,6-difluorophenyl)pyridine-3-carboxamide	IC50	72.1 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-fluorophenyl]-4-methylpyrimidine-5-carboxamide	IC50	81.2 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-fluorophenyl]-2,6-difluorobenzamide	IC50	98.6 nM	US-8921364: Modulators of calcium release-activated calcium channel
4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-N-(2,6-difluorophenyl)-3-fluorobenzamide	IC50	99.7 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-2-methylbenzamide	IC50	120 nM	US-8921364: Modulators of calcium release-activated calcium channel
4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-N-(2,6-difluorophenyl)benzamide	IC50	124 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-3,5-dimethyl-1,2-oxazole-4-carboxamide	IC50	124 nM	US-8921364: Modulators of calcium release-activated calcium channel
3,5-dichloro-N-[4-(3,5-dicyclopropylpyrazol-1-yl)phenyl]pyridine-4-carboxamide	IC50	130 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-(3,5-dicyclopropylpyrazol-1-yl)phenyl]pyridine-4-carboxamide	IC50	141 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-(3,5-dicyclopropylpyrazol-1-yl)-3-fluorophenyl]-2,6-difluorobenzamide	IC50	145 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-fluorophenyl]-2-methylbenzamide	IC50	147 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[6-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-pyridinyl]-4-methylthiadiazole-5-carboxamide	IC50	150 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-fluorophenyl]-3-fluoropyridine-4-carboxamide	IC50	159 nM	US-8921364: Modulators of calcium release-activated calcium channel
3,5-dichloro-N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-fluorophenyl]pyridine-4-carboxamide	IC50	159 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-(4-chloro-3,5-dicyclopropylpyrazol-1-yl)-3-fluorophenyl]-4-methylthiadiazole-5-carboxamide	IC50	181 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-4-methylthiadiazole-5-carboxamide	IC50	184 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-(3,5-dicyclopropylpyrazol-1-yl)-3-fluorophenyl]pyridine-4-carboxamide	IC50	185 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[4-chloro-5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-4-methyl-1,3-thiazole-5-carboxamide	IC50	194 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-fluorophenyl]pyridine-3-carboxamide	IC50	206 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-(3,5-dicyclopropylpyrazol-1-yl)phenyl]-4-methyl-1,3-thiazole-5-carboxamide	IC50	207 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-(3,5-dicyclopropylpyrazol-1-yl)-3-fluorophenyl]-4-methylpyrimidine-5-carboxamide	IC50	224 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]-3-fluorophenyl]pyridine-4-carboxamide	IC50	232 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-(3,5-dicyclopropylpyrazol-1-yl)phenyl]-3-fluoropyridine-4-carboxamide	IC50	244 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]pyridine-4-carboxamide	IC50	255 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-(3,5-dicyclopropylpyrazol-1-yl)phenyl]-5-methyl-1,2-oxazole-4-carboxamide	IC50	256 nM	US-8921364: Modulators of calcium release-activated calcium channel
1-[4-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-3-(4-methyl-1,3-thiazol-5-yl)urea	IC50	269 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[2-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]pyrimidin-5-yl]-2,6-difluorobenzamide	IC50	295 nM	US-8921364: Modulators of calcium release-activated calcium channel
N-[4-[5-(fluoromethyl)-3-(trifluoromethyl)pyrazol-1-yl]phenyl]-4-methyl-1,3-thiazole-5-carboxamide	IC50	373 nM	US-8921364: Modulators of calcium release-activated calcium channel

ChEMBL bioactivities

56 potent at pChembl≥5 of 56 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.69	IC50	20.37	nM	CHEMBL3666849
7.68	IC50	20.79	nM	CHEMBL3666859
7.64	IC50	22.96	nM	CHEMBL3666871
7.49	IC50	32.59	nM	CHEMBL3666861
7.47	IC50	34.11	nM	CHEMBL3666854
7.45	IC50	35.72	nM	CHEMBL3666857
7.44	IC50	36.35	nM	CHEMBL3666830
7.42	IC50	37.58	nM	CHEMBL3666877
7.33	IC50	47.21	nM	CHEMBL3666875
7.32	IC50	48.22	nM	CHEMBL3666851
7.32	IC50	48.02	nM	CHEMBL3666852
7.32	IC50	48.17	nM	CHEMBL3666858
7.30	IC50	50.58	nM	CHEMBL3666874
7.28	IC50	52.62	nM	CHEMBL3666881
7.22	IC50	60.31	nM	CHEMBL3639657
7.22	IC50	60	nM	CHEMBL3666872
7.21	IC50	62.44	nM	CHEMBL3666827
7.20	IC50	63.17	nM	CHEMBL3666845
7.20	IC50	62.56	nM	CHEMBL3666876
7.18	IC50	65.49	nM	CHEMBL3666842
7.15	IC50	70.32	nM	CHEMBL3666873
7.14	IC50	72.03	nM	CHEMBL3666844
7.14	IC50	72.11	nM	CHEMBL3666878
7.09	IC50	81.25	nM	CHEMBL3666867
7.01	IC50	98.58	nM	CHEMBL3666862
7.00	IC50	99.71	nM	CHEMBL3666869
6.92	IC50	119.7	nM	CHEMBL3666847
6.91	IC50	124.5	nM	CHEMBL3666846
6.91	IC50	123.8	nM	CHEMBL3666855
6.89	IC50	129.6	nM	CHEMBL3666833
6.85	IC50	141.3	nM	CHEMBL3666831
6.84	IC50	145.1	nM	CHEMBL3666836
6.83	IC50	147.2	nM	CHEMBL3666860
6.83	IC50	149.6	nM	CHEMBL3666870
6.80	IC50	159.1	nM	CHEMBL3666865
6.80	IC50	159.3	nM	CHEMBL3666866
6.74	IC50	181.1	nM	CHEMBL3666839
6.74	IC50	183.6	nM	CHEMBL3666843
6.73	IC50	184.6	nM	CHEMBL3666837
6.71	IC50	194	nM	CHEMBL3666856
6.69	IC50	205.7	nM	CHEMBL3666863
6.68	IC50	206.7	nM	CHEMBL3666828
6.65	IC50	223.5	nM	CHEMBL3666838
6.63	IC50	232	nM	CHEMBL3666864
6.61	IC50	243.9	nM	CHEMBL3666832
6.59	IC50	256.1	nM	CHEMBL3666829
6.59	IC50	254.7	nM	CHEMBL3666848
6.57	IC50	269	nM	CHEMBL3666853
6.53	IC50	295.4	nM	CHEMBL3666879
6.43	IC50	373.4	nM	CHEMBL3666880

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases methylation	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
beta-lapachone	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
abrine	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Vanadates	decreases expression	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3705678	Binding	In-Vitro Inhibition Assay: Inhibition of CRAC channels was determined following thapsigargin (Sigma, Cat # T9033) induced endoplasmic calcium release in Jurkat cells. (see Yasurio Yonetoky et. al Bio. & Med. Chem. 14 (2006) 4750-4760). Cell	Modulators of calcium release-activated calcium channel

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02737384	PHASE2	TERMINATED	Hematopoietic Stem Cells Transplantation in Children With Combined Immunodeficiency (CID)
NCT02915406	Not specified	NO_LONGER_AVAILABLE	cliniMACs HUD for T Cell Depletion
NCT04902807	Not specified	RECRUITING	Conception of a Diagnosis, Prognosis and Therapeutic Decision Tool for Patients With Autoimmunity and Inflammation
NCT06659588	Not specified	RECRUITING	Study of Populations at Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients With Primary Immunodeficiency and Secondary Humoral Deficiency
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.