CFAP276

Summary

CFAP276 (cilia and flagella associated protein 276, HGNC:32331) is a protein-coding gene on chromosome 1p13.3, encoding Cilia- and flagella-associated protein 276 (Q5T5A4). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.

Predicted to be involved in flagellated sperm motility. Located in axonemal microtubule.

Source: NCBI Gene 127003 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth disease (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 10 total
• GTEx eGene: eQTL in 17 tissues, sQTL in 9 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.49 (unconstrained)
• MANE Select transcript: NM_001245025
• Interaction hub: 2,789 STRING partners (top 3% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32331
Approved symbol	CFAP276
Name	cilia and flagella associated protein 276
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000179902
Ensembl biotype	protein_coding
OMIM	618682
Entrez	127003

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000369948

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 5: 2

ENST00000369948, ENST00000369942, ENST00000369945, ENST00000369949, ENST00000460065, ENST00000462402, ENST00000866707, ENST00001101085

RefSeq mRNA: 5 — MANE Select: NM_001245025 NM_001122961, NM_001245025, NM_001366200, NM_001366201, NM_001366202

CCDS: CCDS41364, CCDS91015, CCDS91016

Canonical transcript exons

ENST00000369948 — 5 exons

Exon	Start	End
ENSE00001451301	109112599	109112747
ENSE00001623202	109107007	109107122
ENSE00003570229	109107921	109108037
ENSE00003580269	109105951	109106098
ENSE00003676093	109106535	109106659

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 99.74.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2064 / max 475.4436, expressed in 248 samples.

Highest expression (Bgee): uterine tube, bronchial epithelial cell, testis, sperm, olfactory segment of nasal mucosa.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFAP276 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 9 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 26 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	4.6e-90	-0.90	1:109106827:G:A
Testis	sqtl	4.9e-29	+1.13	1:109106827:G:A
Whole Blood	eqtl	7.1e-24	+0.71	1:109115282:A:C
Brain Caudate basal ganglia	eqtl	5.8e-21	-0.65	1:109106827:G:A
Brain Nucleus accumbens basal ganglia	eqtl	3.5e-20	-0.83	1:109106827:G:A
Lung	eqtl	8.0e-20	-0.30	1:109106827:G:A
Brain Hypothalamus	eqtl	4.4e-19	-0.61	1:109106827:G:A
Brain Putamen basal ganglia	eqtl	5.8e-11	-0.87	1:109106827:G:A
Brain Cortex	eqtl	8.3e-10	-0.85	1:109106827:G:A
Brain Cortex	sqtl	3.7e-08	+1.16	1:109121057:C:T
Heart Atrial Appendage	eqtl	3.7e-08	-0.53	1:109099006:C:T
Pituitary	sqtl	5.9e-08	+1.00	1:109088434:C:T
Brain Frontal Cortex BA9	eqtl	1.6e-07	-0.81	1:109106827:G:A
Brain Anterior cingulate cortex BA24	sqtl	5.9e-07	+1.26	1:109106827:G:A
Brain Frontal Cortex BA9	sqtl	8.6e-07	+1.48	1:109106827:G:A
Brain Hippocampus	eqtl	1.1e-06	-0.50	1:109106827:G:A
Brain Spinal cord cervical c-1	eqtl	4.3e-06	-0.75	1:109106827:G:A
Esophagus Muscularis	eqtl	1.9e-05	-0.35	1:109106827:G:A
Brain Anterior cingulate cortex BA24	eqtl	2.3e-05	-0.75	1:109106827:G:A
Thyroid	eqtl	4.2e-05	+0.37	1:109105830:C:T

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
13672	0.9574	176
13673	0.5521	109
13676	0.4466	78
13675	0.1303	11
13674	0.0961	33
13671	0.0239	8

Top tissues by expression

showing 100 of 252 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.74	gold quality
bronchial epithelial cell	CL:0002328	99.16	gold quality
left testis	UBERON:0004533	98.67	gold quality
sperm	CL:0000019	98.64	gold quality
right testis	UBERON:0004534	98.55	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.15	gold quality
bronchus	UBERON:0002185	97.94	gold quality
oviduct epithelium	UBERON:0004804	96.54	gold quality
testis	UBERON:0000473	95.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.37	gold quality
fallopian tube	UBERON:0003889	92.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.37	gold quality
adult organism	UBERON:0007023	91.36	gold quality
nasal cavity epithelium	UBERON:0005384	89.48	gold quality
caudate nucleus	UBERON:0001873	88.25	gold quality
nucleus accumbens	UBERON:0001882	87.49	gold quality
right lung	UBERON:0002167	86.05	gold quality
epithelium of nasopharynx	UBERON:0001951	85.73	silver quality
hypothalamus	UBERON:0001898	84.42	gold quality
putamen	UBERON:0001874	84.10	gold quality
pituitary gland	UBERON:0000007	83.01	gold quality
adenohypophysis	UBERON:0002196	82.90	gold quality
amygdala	UBERON:0001876	82.52	gold quality
anterior cingulate cortex	UBERON:0009835	80.45	gold quality
nasal cavity mucosa	UBERON:0001826	80.35	gold quality
ventricular zone	UBERON:0003053	79.70	gold quality
prefrontal cortex	UBERON:0000451	79.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.82	gold quality
right frontal lobe	UBERON:0002810	78.67	gold quality
left uterine tube	UBERON:0001303	78.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.99	gold quality
forebrain	UBERON:0001890	77.59	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.23	gold quality
Ammon’s horn	UBERON:0001954	76.71	gold quality
spinal cord	UBERON:0002240	76.71	gold quality
cardiac muscle of right atrium	UBERON:0003379	75.37	gold quality
left ventricle myocardium	UBERON:0006566	75.05	gold quality
neocortex	UBERON:0001950	74.97	gold quality
frontal cortex	UBERON:0001870	74.57	gold quality
brain	UBERON:0000955	74.50	gold quality
cerebral cortex	UBERON:0000956	74.15	gold quality
kidney epithelium	UBERON:0004819	73.94	gold quality
ganglionic eminence	UBERON:0004023	73.20	gold quality
trachea	UBERON:0003126	72.33	gold quality
temporal lobe	UBERON:0001871	71.75	gold quality
caput epididymis	UBERON:0004358	71.49	gold quality
substantia nigra	UBERON:0002038	71.10	gold quality
endocervix	UBERON:0000458	70.54	gold quality
endometrium	UBERON:0001295	69.42	gold quality
midbrain	UBERON:0001891	69.36	gold quality
upper lobe of left lung	UBERON:0008952	68.68	gold quality
vastus lateralis	UBERON:0001379	68.62	gold quality
quadriceps femoris	UBERON:0001377	68.33	gold quality
islet of Langerhans	UBERON:0000006	68.14	gold quality
superficial temporal artery	UBERON:0001614	67.18	gold quality
upper lobe of lung	UBERON:0008948	66.82	gold quality
body of pancreas	UBERON:0001150	65.93	gold quality
cardiac atrium	UBERON:0002081	65.38	gold quality
pancreas	UBERON:0001264	65.19	gold quality
right atrium auricular region	UBERON:0006631	65.01	gold quality
cortical plate	UBERON:0005343	64.57	gold quality
lung	UBERON:0002048	64.25	gold quality
lateral globus pallidus	UBERON:0002476	63.48	gold quality
superior vestibular nucleus	UBERON:0007227	63.39	silver quality
pancreatic ductal cell	CL:0002079	63.09	silver quality
smooth muscle tissue	UBERON:0001135	62.27	gold quality
mucosa of stomach	UBERON:0001199	61.54	gold quality
myocardium	UBERON:0002349	61.43	gold quality
parotid gland	UBERON:0001831	60.93	gold quality
uterus	UBERON:0000995	60.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	60.28	gold quality
Brodmann (1909) area 46	UBERON:0006483	60.23	gold quality
uterine cervix	UBERON:0000002	59.89	gold quality
cerebellar vermis	UBERON:0004720	59.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	59.48	gold quality
cerebellar cortex	UBERON:0002129	59.38	gold quality
metanephros cortex	UBERON:0010533	59.30	gold quality
cerebellar hemisphere	UBERON:0002245	59.21	gold quality
corpus callosum	UBERON:0002336	59.20	gold quality
muscle layer of sigmoid colon	UBERON:0035805	59.13	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	59.03	gold quality
primary visual cortex	UBERON:0002436	58.82	gold quality
body of stomach	UBERON:0001161	58.48	gold quality
cerebellum	UBERON:0002037	58.39	gold quality
superior frontal gyrus	UBERON:0002661	58.38	gold quality
endothelial cell	CL:0000115	58.10	gold quality
left lobe of thyroid gland	UBERON:0001120	57.62	gold quality
cauda epididymis	UBERON:0004360	57.38	gold quality
stomach	UBERON:0000945	57.22	gold quality
ventral tegmental area	UBERON:0002691	57.09	gold quality
thyroid gland	UBERON:0002046	57.05	gold quality
lower esophagus muscularis layer	UBERON:0035833	56.94	gold quality
subthalamic nucleus	UBERON:0001906	56.91	gold quality
lower esophagus	UBERON:0013473	56.77	gold quality
dorsal plus ventral thalamus	UBERON:0001897	56.61	gold quality
substantia nigra pars compacta	UBERON:0001965	56.56	gold quality
substantia nigra pars reticulata	UBERON:0001966	56.34	gold quality
occipital lobe	UBERON:0002021	56.29	gold quality
postcentral gyrus	UBERON:0002581	56.23	gold quality
metanephros	UBERON:0000081	56.20	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	2898.10
E-HCAD-1	yes	2074.39
E-MTAB-8221	yes	1982.56
E-MTAB-6701	yes	1746.34
E-CURD-114	yes	1715.18
E-GEOD-130148	yes	1515.30
E-HCAD-38	yes	1465.50
E-MTAB-10287	yes	1413.14
E-MTAB-9154	yes	1298.27
E-MTAB-10485	yes	560.17
E-GEOD-134144	yes	30.60
E-MTAB-9388	yes	7.85
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Group enriched

60 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	106.2	medium
Fallopian tube	tissue	100.1	high
Choroid plexus	tissue	27.7	medium
Periaqueductal gray	tissue	14.2
Basal ganglia	tissue	10.9	not detected
Hypothalamus	tissue	10.7
Septum	tissue	10.0
Ventral forebrain	tissue	8.5
Amygdala	tissue	8.2
Hippocampal formation	tissue	8.1
Prefrontal cortex	tissue	7.0
Cerebral cortex	tissue	7.0	not detected
Pons	tissue	6.6
Putamen	tissue	6.6
Temporal cortex	tissue	6.2
Entorhinal cortex	tissue	5.5
Motor cortex	tissue	5.4
Insular cortex	tissue	5.2
Thalamus	tissue	4.9
Retrosplenial and cingulate cortex	tissue	4.9
Caudate putamen	tissue	4.7
Olfactory bulb	tissue	4.4
Occipital cortex	tissue	4.4
Midbrain	tissue	4.3
Medulla oblongata	tissue	4.3
Corpus callosum	tissue	4.3
Somatosensory cortex	tissue	4.2
Retrosplenial cortex	tissue	4.1
Lung	tissue	3.6	not detected
Cerebellum	tissue	3.4	not detected
Spinal cord	tissue	3.4
Substantia nigra	tissue	3.3
Superior colliculi	tissue	2.9
Frontal cortex	tissue	2.8
Pituitary gland	tissue	2.3
Nucleus accumbens	tissue	1.5
Hippocampus	tissue	1.5	not detected
Locus coeruleus	tissue	1.3
Postcentral gyrus	tissue	1.3
Epididymis	tissue	1.2	not detected
Cervix	tissue	1.0	not detected
Endometrium 1	tissue	1.0	low
Pancreas	tissue	0.8	not detected
Urinary bladder	tissue	0.3	not detected
Thyroid gland	tissue	0.3	not detected
Duodenum	tissue	0.3	not detected
Thymus	tissue	0.3
Breast	tissue	0.2	not detected
Stomach 1	tissue	0.2	not detected
Retina	tissue	0.2
Parathyroid gland	tissue	0.2	not detected
Prostate	tissue	0.2	not detected
Skin 1	tissue	0.1	not detected
Esophagus	tissue	0.1	not detected
Rectum	tissue	0.1	not detected
Smooth muscle	tissue	0.1	not detected
Small intestine	tissue	0.1	not detected
Adrenal gland	tissue	0.1	not detected
Nasopharynx	tissue	-1.0	high
Bronchus	tissue	-1.0	high

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Dorsal hippocampus (8.1), Ventral hippocampus (8.0), Subiculum (7.8), Nucleus tractus solitarii (5.2), Periaquaductal grey, lateral (4.8).

Regulation

Is transcription factor: no

Functional genomics

gnomAD constraint: pLI 6.37e-09, LOEUF 1.49, missense Z 0.662 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000369948 — one region, missense o/e 0.92.

Literature-anchored findings (GeneRIF, showing 2)

• the identification of two heterozygous missense mutations in the C1orf194 gene at 1p21.2-p13.2 with Charcot-Marie-Tooth disease are reported (PMID:31199454)
• C1orf194 deficiency leads to incomplete early embryonic lethality and dominant intermediate Charcot-Marie-Tooth disease in a knockout mouse model. (PMID:32592472)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-163l21.7	ENSDARG00000034457
mus_musculus	Cfap276	ENSMUSG00000027886
rattus_norvegicus	Cfap276	ENSRNOG00000020307

Paralogs (4): FLVCR2 (ENSG00000119686), SLC49A4 (ENSG00000138463), FLVCR1 (ENSG00000162769), SLC49A3 (ENSG00000169026)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1922754) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 28 distinct phenotype terms.

Mouse phenotype (MP)	Records
demyelination	2
impaired coordination	2
abnormal gait	2
short stride length	2
limb grasping	2
abnormal sciatic nerve morphology	2
abnormal myelin sheath morphology	2
abnormal action potential	2
axon degeneration	2
decreased grip strength	2
abnormal internode morphology	2
increased myelin sheath thickness	2
decreased motor neuron number	1
decreased body weight	1
abnormal embryo development	1
decreased embryo size	1
abnormal placenta morphology	1
impaired embryo implantation	1
abnormal motor capabilities/coordination/movement	1
muscular atrophy	1
abnormal physical strength	1
reproductive system phenotype	1
hyporesponsive to tactile stimuli	1
decreased nerve conduction velocity	1
skeletal muscle fiber atrophy	1

+3 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	E1B9I5	83.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
TMEM167B	protein-coding	56900
ELAPOR1	protein-coding	57535
SCARNA2	ncRNA	677766
CELSR2	protein-coding	1952
SARS1	protein-coding	6301
PSRC1	protein-coding	84722
TMEM167B-DT	ncRNA	105378892

Protein

Protein identifiers

Cilia- and flagella-associated protein 276 — Q5T5A4 (reviewed: Q5T5A4)

All UniProt accessions (4): B1ALJ5, E9PLX1, E9PRR4, Q5T5A4

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. May play an important role for the maintenance of myelin-axon integrity. May affect intracellular Ca(2+) homeostasis.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules.

Subcellular location. Cytoplasm. Cytoskeleton. Flagellum axoneme. Cilium axoneme.

Tissue specificity. Expressed in cerebrum, cerebellum, gastrocnemius muscle, spinal cord and lung tissues.

Disease relevance. CFAP276 mutations may be the cause of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. Intermediate forms of Charcot-Marie-Tooth disease exist and are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5T5A4-1	1	yes
Q5T5A4-2	2

RefSeq proteins (5): NP_001116433, NP_001231954, NP_001353129, NP_001353130, NP_001353131 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022179	CFAP276	Family

Pfam: PF12494

UniProt features (8 total): region of interest 2, compositionally biased region 2, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
7UNG	48-nm repeat of the human respiratory doublet microtubule	ELECTRON MICROSCOPY	3.6
8J07	96nm repeat of human respiratory doublet microtubule and associated axonemal complexes	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T5A4-F1	67.55	0.03

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): end piece; mid piece; principal piece

Antibody reliability (HPA): IH enhanced · IF approved

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 63 (showing top): BENPORATH_ES_WITH_H3K27ME3, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, GOCC_CYTOPLASMIC_MICROTUBULE, GOCC_CILIUM, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOCC_AXONEMAL_MICROTUBULE, GOCC_9PLUS2_MOTILE_CILIUM, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_POLYMERIC_CYTOSKELETAL_FIBER, GOCC_SUPRAMOLECULAR_POLYMER, FOXJ2_TARGET_GENES

GO Biological Process (1): flagellated sperm motility (GO:0030317)

GO Cellular Component (6): cytoplasm (GO:0005737), cytoskeleton (GO:0005856), axonemal microtubule (GO:0005879), sperm flagellum (GO:0036126), axonemal B tubule inner sheath (GO:0160112), axoneme (GO:0005930)

GO top-level categories

14 GO namespaces:

Category	Terms
cellular anatomical structure	3
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
cytoplasmic microtubule	1
axoneme	1
9+2 motile cilium	1
A axonemal microtubule	1
axonemal microtubule doublet inner sheath	1
cytoskeleton	1
microtubule	1
ciliary plasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 7 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
axonemal microtubule	CC	direct assay
cytoplasm	CC	direct assay
cytoskeleton	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 2,789 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFAP276	UQCR10	Q9UDW1	605
CFAP276	RIBC1	Q8N443	574
CFAP276	BOD1L2	Q8IYS8	570
CFAP276	ZMYND12	Q9H0C1	566
CFAP276	SAXO2	Q658L1	543
CFAP276	CFAP57	Q96MR6	530
CFAP276	CFAP52	Q8N1V2	521
CFAP276	ANKFN1	Q8N957	518
CFAP276	DNAJC16	Q9Y2G8	513
CFAP276	VWA8	A3KMH1	502
CFAP276	IFT56	A0AVF1	498
CFAP276	DRC2	Q8IXS2	488
CFAP276	TEX38	Q6PEX7	482
CFAP276	OR7G2	Q8NG99	477
CFAP276	NME7	Q9Y5B8	475

Disease & clinical

Genetic variants

Variant evidence for CFAP276: 10 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 241):

Position(s)	Effect	Δscore	Sites
1:109106533–109106534	donor_loss	1.0000	5
1:109106099–109106100	acceptor_loss	0.9900	6
1:109106660–109106661	acceptor_loss	0.9900	6
1:109106672	acceptor_gain	0.9900	2
1:109106101	acceptor_gain	0.9800
1:109108709	donor_gain	0.9800
1:109112597–109112598	donor_loss	0.9600	4
1:109112597–109112598	donor_loss	0.9500	2
1:109112599	donor_loss	0.9300
1:109112599	donor_loss	0.9200

AlphaMissense

162 missense substitutions predicted likely pathogenic (of 1,106 scored), across 48 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H150	8	0.838	0.941
D70	8	0.803	0.913
D73	8	0.766	0.844
F167	7	0.919	0.979
W131	7	0.824	0.934
W44	7	0.780	0.933
G157	6	0.806	0.918
Y158	5	0.865	0.944
F166	5	0.864	0.946
K161	5	0.823	0.888
G164	5	0.804	0.900
D163	5	0.698	0.788
F74	4	0.792	0.815
G144	4	0.761	0.851
N155	4	0.750	0.833
Y80	4	0.744	0.845
L47	4	0.683	0.788
F87	4	0.666	0.700
R160	3	0.922	0.967
S141	3	0.855	0.855

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Uterine Corpus Endometrial Carcinoma)

Disease associations

OMIM: gene MIM:618682 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
Charcot-Marie-Tooth disease	Limited	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
Hereditary neuropathy	green
Hereditary neuropathy or pain disorder	green

Mondo (1): Charcot-Marie-Tooth disease (MONDO:0015626)

GWAS associations

1 associations:

Study	Trait	p-value
GCST90011900_101	Serum alkaline phosphatase levels	1e-12

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aflatoxin B2	decreases methylation	1
tebuconazole	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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

59 trials:

NCT	Phase	Status	Title
NCT04762758	Phase 3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT00271635	Phase 2	COMPLETED	Ascorbic Acid Treatment in CMT1A Trial (AATIC)
NCT01401257	Phase 2	COMPLETED	Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
NCT02561702	Phase 2	COMPLETED	Mexiletine for Muscle Cramps in Charcot Marie Tooth Disease
NCT02967679	Phase 2	COMPLETED	SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
NCT03124459	Phase 2	TERMINATED	Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease
NCT03254199	Phase 2	TERMINATED	A Study to Assess the Safety and Effectiveness of FLX-787 in Subjects With Charcot-Marie-Tooth Disease Experiencing Muscle Cramps.
NCT03943290	Phase 2	TERMINATED	Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)
NCT05777226	Phase 2	UNKNOWN	Research of SORD-CMT Natural History and Epalrestat Treatment
NCT06482437	Phase 2	COMPLETED	Safety and Efficacy of NMD670 in Adult Patients With Type 1 and Type 2 Charcot-Marie-Tooth Disease
NCT01289704	Phase 2/3	UNKNOWN	Treadmill, Stretching and Proprioceptive Exercise (TreSPE) Rehabilitation Program for Charcot-Marie-Tooth Neuropathy Type 1A (CMT1A)
NCT00541164	Phase 1/2	COMPLETED	Effects of Coenzyme Q10 on Charcot-Marie-Tooth Disease
NCT05361031	Phase 1/2	COMPLETED	The Safety and Tolerability of Engensis (VM202) in Patients With Charcot-Marie-Tooth Disease Subtype 1A (CMT1A)
NCT07223632	Phase 1/2	ACTIVE_NOT_RECRUITING	Treatment of Charcot-Marie-Tooth Disease, Axonal, Type 2S (CMT2S) in an Individual Patient
NCT00149045	Not specified	COMPLETED	Follow up and Observation of Charcot Marie Tooth Disease in Families
NCT01193075	Not specified	RECRUITING	Natural History Evaluation of Charcot Marie Tooth Disease (CMT) Types CMT1B, CMT2A, CMT4A, CMT4C, and Others
NCT01203085	Not specified	COMPLETED	Development of Charcot Marie Tooth Disease (CMT) Pediatric Scale for Children With CMT
NCT01455623	Not specified	COMPLETED	Development and Validation of a Disability Severity Index for CMT
NCT01918826	Not specified	COMPLETED	Evaluation of the Analgesic Efficiency of the Transcutaneous Neurostimulation in the Charcot Syndrome Marie Tooth on the Pains of Lower Limbs
NCT02001038	Not specified	COMPLETED	Survey of Current Management of Orthopaedic Complications in CMT Patients
NCT02011204	Not specified	COMPLETED	Study of Electrical Impedance Myography (EIM) in ALS
NCT02194010	Not specified	COMPLETED	Disability Severity Scale (DSI) and Hereditary Motor and Sensory Neuropathy Overall Disability Scale (HMSN-R-ODS)
NCT02429947	Not specified	COMPLETED	An Analysis of the Symptomatic Domains Most Relevant to Charcot Marie Tooth Neuropathy (CMT) Patients
NCT02532244	Not specified	COMPLETED	Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT02788734	Not specified	COMPLETED	Patient Reported Outcomes Measures (PROM) in Carpal Tunnel Therapies in Patients With Inherited Neuropathies
NCT02979145	Not specified	UNKNOWN	Charcot-Marie-Tooth Disease (CMT) Infant Scale (INC-6611)
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03460951	Not specified	COMPLETED	Diffusion Tensor Imaging in Chronic Inflammatory Demyelinating Polyneuropathy (PIDC)
NCT03715283	Not specified	COMPLETED	Change in MUNIX in Patients With CMT1A Undergoing a Home Ankle Strengthening Program Versus Standard of Care
NCT03782883	Not specified	COMPLETED	The Impact of Charcot-Marie-Tooth Disease in the Real World
NCT03810508	Not specified	TERMINATED	A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J)
NCT03966287	Not specified	COMPLETED	Analysis of Pain and Quality of Life in Patients With Charcot-Marie-Tooth Neuropathy (CMT)
NCT04010188	Not specified	RECRUITING	A Registered Cohort Study on Charcot-Marie-Tooth Disease
NCT04283175	Not specified	COMPLETED	Validation Study of Posturology Platforms for Evaluating Postural Control of Hemiparetic and Neuro-muscular Patients
NCT04461613	Not specified	UNKNOWN	Physical Activity in Persons With Charcot-Marie-Tooth: Developing a Measurement Instrument
NCT04786522	Not specified	COMPLETED	Irisin Levels in Patients With Charcot-Marie-Tooth (CMT) Disease
NCT04967716	Not specified	UNKNOWN	Genetics of Charcot-Marie-Tooth Dystrophy and Related Diseases
NCT04980807	Not specified	COMPLETED	Observational Study of Neuromuscular Function in CMT Type 1&2 and Healthy Controls
NCT05011006	Not specified	TERMINATED	NT-3 Levels and Function in Individuals With CMT
NCT05827419	Not specified	TERMINATED	Hearing and Balance Disorders in Peripheral Neuropathy
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease
NCT06203093	Not specified	UNKNOWN	Charcot-Marie-Tooth Disease (CMT) Biological Sample Collection for IPSC Generation and Biobanking
NCT06666816	Not specified	RECRUITING	Observational Study to Observe Variations of Gait Parameters in Patients With Neuromuscular Diseases
NCT06708468	Not specified	RECRUITING	Personalized Training for People With Rare Neuromuscular Disorders
NCT06794489	Not specified	RECRUITING	Longitudinal Biomarkers With Selected Outcome Measures In CMT
NCT06808581	Not specified	COMPLETED	EVALUATION OF SERUM INFLAMMATORY CYTOKINE CONCENTRATION IN HEREDITARY SENSITIVOMOTOR NEUROPATHIES
NCT06881979	Not specified	RECRUITING	High-Tech Rehabilitation Pathway for Chronic Adult Neuromuscular Diseases - Fit4MedRob-Chronic MND Project
NCT06945835	Not specified	COMPLETED	High Intensity Exercise and Improving Physical Activity Among People With Neurologic Dysfunction
NCT07038239	Not specified	RECRUITING	Genotype/Phenotype Correlation of MORC2 Mutations
NCT07072676	Not specified	ENROLLING_BY_INVITATION	The Use of Assistive Gait Devices Can Reduce the Risk of Falls in Patients With Neuromuscular Diseases Following a Training Period.
NCT07136844	Not specified	RECRUITING	Gait Analysis Parameter and Upper Limb Evaluation in Adult Patients With Neurological or Metabolic Pathology
NCT07152197	Not specified	RECRUITING	Effects of Resistance Exercises in Hereditary Sensory-Motor Neuropathy (Charcot-Marie-Tooth Disease)
NCT07188415	Not specified	RECRUITING	CMT Gait, Mobility, Balance - AOFAS Grant
NCT07432035	Not specified	NOT_YET_RECRUITING	Walking Function Outcomes Following Surgical Correction With Rehabilitation Versus Physical Therapy Alone in Charcot-Marie-Tooth Disease: A Bidirectional Cohort Study
NCT07476365	Not specified	RECRUITING	A Multi-omic Approach to the Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease (CMT1A)
NCT07478172	Not specified	RECRUITING	Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
NCT07570446	Not specified	RECRUITING	AUTONOMOUS DISORDERS IN CMT
NCT07570459	Not specified	RECRUITING	TREMOR IN CHARCOT-MARIE-TOOTH