severe combined immunodeficiency due to CORO1A deficiency

Summary

severe combined immunodeficiency due to CORO1A deficiency (MONDO:0014168) is a disease caused by CORO1A (GenCC Definitive), with 6 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: CORO1A (GenCC Definitive)
• Cohort genes: 6
• ClinVar variants: 345

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		9	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	severe combined immunodeficiency due to CORO1A deficiency
Mondo ID	MONDO:0014168
OMIM	615401
Orphanet	228003
DOID	DOID:0060019
ICD-11	575769539
UMLS	C3809383
MedGen	815713
GARD	0017144
Is cancer (heuristic)	no

Also known as: coronin-1A deficiency · IMD8 · immunodeficiency 8 · immunodeficiency type 8 · SCID due to CORO1A deficiency · SCID due to coronin-1A deficiency · severe combined immunodeficiency due to CORO1A deficiency · severe combined immunodeficiency due to coronin-1A deficiency

Data availability: 345 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › combined immunodeficiency › severe combined immunodeficiency › T-B+ severe combined immunodeficiency › severe combined immunodeficiency due to CORO1A deficiency

Related subtypes (9): T-B+ severe combined immunodeficiency due to gamma chain deficiency, combined immunodeficiency, X-linked, T-B+ severe combined immunodeficiency due to JAK3 deficiency, immunodeficiency 104, lung fibrosis-immunodeficiency-46,XX gonadal dysgenesis syndrome, T-B+ severe combined immunodeficiency due to IL-7Ralpha deficiency, T-B+ severe combined immunodeficiency due to CD45 deficiency, T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta, severe combined immunodeficiency due to LAT deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

345 retrieved; paginated sample, class counts are floors:

205 likely benign, 102 uncertain significance, 14 pathogenic, 9 benign, 7 likely pathogenic, 5 benign/likely benign, 3 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
424756	NM_007074.3(CORO1A):c.[1078delC];[248_249delCT]		Pathogenic	criteria provided, single submitter
1074667	NC_000016.9:g.(?_30196531)_30199897del	CORO1A	Pathogenic	criteria provided, single submitter
1381990	NM_007074.4(CORO1A):c.855_856del (p.Cys285fs)	CORO1A	Pathogenic	criteria provided, single submitter
157509	NM_007074.4(CORO1A):c.1078del (p.Gln360fs)	CORO1A	Pathogenic	criteria provided, single submitter
2104536	NM_007074.4(CORO1A):c.517G>T (p.Glu173Ter)	CORO1A	Pathogenic	criteria provided, single submitter
3658357	NM_007074.4(CORO1A):c.3G>A (p.Met1Ile)	CORO1A	Pathogenic	criteria provided, single submitter
40886	NM_007074.4(CORO1A):c.248_249del (p.Pro83fs)	CORO1A	Pathogenic	criteria provided, single submitter
4291916	NM_007074.4(CORO1A):c.1060C>T (p.Arg354Ter)	CORO1A	Pathogenic	criteria provided, single submitter
64645	NM_007074.4(CORO1A):c.400G>A (p.Val134Met)	CORO1A	Pathogenic	no assertion criteria provided
663029	NM_007074.4(CORO1A):c.674_677del (p.Arg225fs)	CORO1A	Pathogenic	criteria provided, single submitter
658983	NC_000016.10:g.(?30066878)(30188984_?)del	LOC125146441	Pathogenic	criteria provided, single submitter
541425	NC_000016.10:g.(?30066878)(30188596_?)del	LOC130058813	Pathogenic	criteria provided, single submitter
973590	NM_001364905.1(LRBA):c.4333C>T (p.Arg1445Ter)	LRBA	Pathogenic	criteria provided, multiple submitters, no conflicts
1054446	NC_000016.9:g.(?29802081)(30199917_?)del	MAZ	Pathogenic	criteria provided, single submitter
1067675	NM_007074.4(CORO1A):c.1007+1G>A	CORO1A	Likely pathogenic	criteria provided, single submitter
1480695	NM_007074.4(CORO1A):c.1065+2T>C	CORO1A	Likely pathogenic	criteria provided, single submitter
2058817	NM_007074.4(CORO1A):c.35G>T (p.Arg12Leu)	CORO1A	Likely pathogenic	criteria provided, single submitter
2809851	NM_007074.4(CORO1A):c.756_756+1del	CORO1A	Likely pathogenic	criteria provided, single submitter
3580046	NM_007074.4(CORO1A):c.696dup (p.Lys233fs)	CORO1A	Likely pathogenic	criteria provided, single submitter
4278190	NM_007074.4(CORO1A):c.382del (p.Glu128fs)	CORO1A	Likely pathogenic	criteria provided, single submitter
973589	NM_001364905.1(LRBA):c.4159-1G>T	LRBA	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452393	NM_007074.4(CORO1A):c.314_315del (p.Thr105fs)	CORO1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
424440	NM_007074.4(CORO1A):c.1189G>A (p.Val397Ile)	CORO1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
827975	NM_007074.4(CORO1A):c.451+7C>T	CORO1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1001473	NM_007074.4(CORO1A):c.1281G>A (p.Ser427=)	CORO1A	Uncertain significance	criteria provided, single submitter
1002221	NM_007074.4(CORO1A):c.580T>A (p.Ser194Thr)	CORO1A	Uncertain significance	criteria provided, multiple submitters, no conflicts
1007111	NM_007074.4(CORO1A):c.973C>T (p.Arg325Cys)	CORO1A	Uncertain significance	criteria provided, single submitter
1013794	NM_007074.4(CORO1A):c.974G>A (p.Arg325His)	CORO1A	Uncertain significance	criteria provided, single submitter
1014798	NM_007074.4(CORO1A):c.23C>T (p.Ser8Phe)	CORO1A	Uncertain significance	criteria provided, single submitter
1024414	NM_007074.4(CORO1A):c.1222C>T (p.Arg408Trp)	CORO1A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
CORO1A	Definitive	Autosomal recessive	severe combined immunodeficiency due to CORO1A deficiency	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CORO1A	Orphanet:228003	Severe combined immunodeficiency due to CORO1A deficiency
LRBA	Orphanet:445018	Syndromic autoimmune enteropathy due to LRBA deficiency

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CORO1A	HGNC:2252	ENSG00000102879	P31146	Coronin-1A	gencc,clinvar
SULT1A3	HGNC:11455	ENSG00000261052	P0DMM9	Sulfotransferase 1A3	clinvar
LRBA	HGNC:1742	ENSG00000198589	P50851	Lipopolysaccharide-responsive and beige-like anchor protein	clinvar
FIMP1	HGNC:26346	ENSG00000167194	Q96LL3	Fertilization-influencing membrane protein	clinvar
BOLA2	HGNC:29488	ENSG00000183336	Q9H3K6	BolA-like protein 2	clinvar
MAZ	HGNC:6914	ENSG00000103495	P56270	Myc-associated zinc finger protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CORO1A	Coronin-1A	May be a crucial component of the cytoskeleton of highly motile cells, functioning both in the invagination of large pieces of plasma membrane, as well as in forming protrusions of the plasma membrane involved in cell locomotion.
SULT1A3	Sulfotransferase 1A3	Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of phenolic monoamines (neurotransmitters such as dopamine, (R)-adrenaline/epinephrine, (R)-noradrenaline/norepinep…
LRBA	Lipopolysaccharide-responsive and beige-like anchor protein	Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules.
FIMP1	Fertilization-influencing membrane protein	May play a role in sperm-oocyte fusion during fertilization.
BOLA2	BolA-like protein 2	Acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins.
MAZ	Myc-associated zinc finger protein	Transcriptional regulator, potentially with dual roles in transcription initiation and termination.

Protein-family classification

Druggable: 1 · Difficult: 3 · Unknown: 2 · Druggable fraction: 0.17

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	2	5.8×	0.172
Enzyme (other)	1	2.0×	0.719
Transcription factor	1	1.4×	0.719
Other/Unknown	2	0.6×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CORO1A	Scaffold/PPI	no		WD40_rpt, DUF1899, Trimer_CC
SULT1A3	Enzyme (other)	yes	2.8.2.1	Sulfotransferase_dom, P-loop_NTPase
LRBA	Scaffold/PPI	no		BEACH_dom, WD40_rpt, NBEA-like_DUF1088
FIMP1	Other/Unknown	no		FIMP
BOLA2	Other/Unknown	no		BolA, BolA-like_sf, BOL2
MAZ	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf

Expression context

Cohort genes with no expression data: 0.

5 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	2
monocyte	2
male germ line stem cell (sensu Vertebrata) in testis	2
leukocyte	1
duodenum	1
mucosa of transverse colon	1
bronchial epithelial cell	1
epithelium of bronchus	1
upper leg skin	1
left testis	1
right testis	1
primordial germ cell in gonad	1
cortical plate	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CORO1A	252	ubiquitous	marker	granulocyte, monocyte, leukocyte
SULT1A3	134		marker	duodenum, mucosa of transverse colon, granulocyte
LRBA	274	ubiquitous	marker	upper leg skin, bronchial epithelial cell, epithelium of bronchus
FIMP1	114		yes	right testis, left testis, male germ line stem cell (sensu Vertebrata) in testis
BOLA2	131		marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, monocyte
MAZ	288	ubiquitous	marker	ventricular zone, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CORO1A	3,620
MAZ	1,839
BOLA2	1,414
LRBA	1,331
SULT1A3	521
FIMP1	317

Structural data

PDB: 2 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SULT1A3	P0DMM9	2
LRBA	P50851	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CORO1A	P31146	93.25
BOLA2	Q9H3K6	92.72
FIMP1	Q96LL3	65.84
MAZ	P56270	60.37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 6 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Prevention of phagosomal-lysosomal fusion	1	423.0×	0.021	CORO1A
Cytosolic sulfonation of small molecules	1	173.0×	0.021	SULT1A3
IRE1alpha activates chaperones	1	173.0×	0.021	SULT1A3
Interleukin-12 family signaling	1	158.6×	0.021	BOLA2
Paracetamol ADME	1	141.0×	0.021	SULT1A3
Interleukin-12 signaling	1	135.9×	0.021	BOLA2
Unfolded Protein Response (UPR)	1	119.0×	0.021	SULT1A3
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	100.2×	0.021	BOLA2
Phase II - Conjugation of compounds	1	92.8×	0.021	SULT1A3
Drug ADME	1	76.1×	0.023	SULT1A3
XBP1(S) activates chaperone genes	1	71.8×	0.023	SULT1A3
Biological oxidations	1	43.3×	0.034	SULT1A3
Signaling by Interleukins	1	21.4×	0.064	BOLA2
Cytokine Signaling in Immune system	1	13.6×	0.092	BOLA2
Cellular responses to stress	1	12.3×	0.095	SULT1A3
Cellular responses to stimuli	1	10.5×	0.104	SULT1A3
Immune System	1	4.3×	0.227	BOLA2
Metabolism	1	3.9×	0.237	SULT1A3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of vesicle fusion	1	1404.3×	0.014	CORO1A
uropod organization	1	1404.3×	0.014	CORO1A
negative regulation of actin nucleation	1	1404.3×	0.014	CORO1A
epinephrine metabolic process	1	936.2×	0.014	SULT1A3
thymocyte migration	1	936.2×	0.014	CORO1A
phagolysosome assembly	1	561.7×	0.016	CORO1A
obsolete early endosome to recycling endosome transport	1	561.7×	0.016	CORO1A
natural killer cell degranulation	1	401.2×	0.016	CORO1A
cellular response to dopamine	1	401.2×	0.016	SULT1A3
flavonoid metabolic process	1	351.1×	0.016	SULT1A3
dopamine catabolic process	1	280.9×	0.016	SULT1A3
serotonin metabolic process	1	280.9×	0.016	SULT1A3
norepinephrine metabolic process	1	255.3×	0.016	SULT1A3
thyroid hormone metabolic process	1	234.1×	0.016	SULT1A3
[2Fe-2S] cluster assembly	1	234.1×	0.016	BOLA2
termination of RNA polymerase II transcription	1	216.1×	0.016	MAZ
nerve growth factor signaling pathway	1	216.1×	0.016	CORO1A
ethanol catabolic process	1	200.6×	0.016	SULT1A3
3’-phosphoadenosine 5’-phosphosulfate metabolic process	1	187.2×	0.016	SULT1A3
leukocyte chemotaxis	1	175.5×	0.016	CORO1A
sulfation	1	175.5×	0.016	SULT1A3
protein localization to phagophore assembly site	1	165.2×	0.016	LRBA
dopamine metabolic process	1	165.2×	0.016	SULT1A3
epithelial cell migration	1	156.0×	0.016	CORO1A
regulation of release of sequestered calcium ion into cytosol	1	156.0×	0.016	CORO1A
positive chemotaxis	1	133.8×	0.018	CORO1A
cell-substrate adhesion	1	127.7×	0.019	CORO1A
positive regulation of T cell migration	1	122.1×	0.019	CORO1A
cellular response to interleukin-4	1	108.0×	0.020	CORO1A
vesicle fusion	1	100.3×	0.020	CORO1A

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 4 of 6 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BOLA2	1	2
CORO1A	0	0
SULT1A3	0	0
LRBA	0	0
FIMP1	0	0
MAZ	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	BOLA2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CORO1A	12	Binding:12
BOLA2	7	Binding:7
SULT1A3	3	ADMET:3
LRBA	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SULT1A3	2.8.2.1	aryl sulfotransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	BOLA2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	1	BOLA2
C	Druggable family + PDB, no drug	1	SULT1A3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	CORO1A, LRBA, FIMP1, MAZ

Undrugged target profiles

5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CORO1A	12	—
SULT1A3	3	—
LRBA	1	—
FIMP1	0	—
MAZ	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.